.. _ABCC8: ABCC8 ^^^^^ .. contents:: :local: General Information ******************* :Full gene name: ATP-binding cassette, sub-family C (CFTR/MRP), member 8 :Entrez Gene ID: 6833 :Location: 11p15.1 :Synonyms: TNDM2, ABC36, HHF1, PHHI, MRP8, HI, SUR, SUR1, HRINS, SUR1delta2 :Type: protein-coding User SNPs ********* SNPs given by the user that are near or inside this gene: +--------+---------------+------------+ | SNP | Distance (bp) | Direction | +========+===============+============+ | rs5215 | 5802 | downstream | +--------+---------------+------------+ .. _ABCC8 Gene summary: NCBI Summary ************ The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a modulator of ATP-sensitive potassium channels and \ ``insulin``\ release. Mutations and deficiencies in this protein have been observed in patients with hyper\ ``insulin``\ emic hypoglycemia of infancy, an autosomal recessive disorder of unregulated and high \ ``insulin``\ secretion. Mutations have also been associated with non-\ ``insulin``\ -dependent \ ``diabetes``\ mellitus type II, an autosomal dominant disease of defective \ ``insulin``\ secretion. Alternative splicing of this gene has been observed; however, the transcript variants have not been fully described. [provided by RefSeq, Jul 2008] .. _OMIM ID 600509 : http://omim.org/entry/600509 .. _ABCC8 OMIM Text: OMIM **** :OMIM ID: `OMIM ID 600509 `_ **Allelic Variants (Selected Examples)** .0001 HYPER\ ``INSULIN``\ EMIC HYPOGLYCEMIA, FAMILIAL, 1 In a child with hyper\ ``INSULIN``\ emic hypoglycemia (256450), born of consanguineous parents, Thomas et al. (1995) showed that a cloned pancreatic cDNA product had a 109-bp deletion within the NBF2 region of SUR, which corresponded to skipping of exon chi. The deletion caused disruption of the NBF2 consensus sequence by generating a frameshift and ultimately a premature stop signal 24 codons past the deletion. In genomic DNA, a homozygous G-to-A point mutation was found in the 3-prime end of the skipped exon. The recognition site for the restriction endonuclease MspI was destroyed by this base change. Both affected children in the family were homozygous, whereas the parents and 2 unaffected sibs were heterozygous. Twelve other affected children from 6 families of Saudi Arabian origin and 1 family of German origin were homozygous for the G-to-A point mutation, as demonstrated by loss of the MspI recognition site. The G-to-A mutation involved the last nucleotide of the skipped exon. Thomas et al. (1995) cited other instances in which G-to-A point mutations at this position had been observed to result in skipping of the exon containing the mutation. .0002 HYPER\ ``INSULIN``\ EMIC HYPOGLYCEMIA, FAMILIAL, 1 In 2 sibs with hyper\ ``INSULIN``\ emic hypoglycemia (256450), born of consanguineous parents, Thomas et al. (1995) found a mutation in the 3-prime splice site sequence preceding the NBF2 region. The G-to-A mutation destroyed an NciI restriction endonuclease recognition site, and homozygous loss of this site cosegregated with disease phenotype within the family. The G-to-A transition occurred at the ninth nucleotide from the 3-prime end of the intron preceding exon alpha, the first NBF2 exon. In a construct containing the mutation, 3 cryptic 3-prime splice sites within exon alpha were used in place of the wildtype splicing site. Nestorowicz et al. (1996) demonstrated that this mutation in the SUR1 gene and the F1388del mutation (600509.0006) account for approximately 88% of hyper\ ``INSULIN``\ ism-associated chromosomes in Ashkenazi Jewish patients. Haplotype analysis with microsatellite markers flanking the gene revealed that the delF1388 mutation, reported only in Ashkenazi probands, occurred on 2 related extended haplotypes. By contrast, the second, more common mutation (3992-9G-A) was associated with 9 different intergenic haplotypes and was reported in non-Jewish hyper\ ``INSULIN``\ ism patients as well. Glaser et al. (1999) evaluated disease-associated chromosomes from 41 Ashkenazi Jewish and 2 non-Jewish hyper\ ``INSULIN``\ ism patients carrying the 3992-9G-A mutation by assessing haplotypes defined by 9 common single-nucleotide polymorphisms (SNPs), 6 in the SUR1 gene and 3 in the closely linked KIR6.2 gene. They found that all 54 chromosomes carrying this particular mutation in the Jewish patients appeared to have originated from 1 founder mutation, whereas the same mutation in chromosomes from non-Jewish patients originated independently. .0003 HYPER\ ``INSULIN``\ EMIC HYPOGLYCEMIA, FAMILIAL, 1 In a boy with hyper\ ``INSULIN``\ emic hypoglycemia (256450), born of consanguineous Malaysian parents, Thomas et al. (1996) found that the 6 exons that compose the NBF2 region of SUR had wildtype sequence. The NBF1 region, which is encoded by 8 exons that span approximately 8.2 kb of genomic sequence, shows strong homology with the NBF2 region and the NBF regions of other superfamily members. In of the proband of this family, a homozygous G-to-T transversion was found in the second exon (106-bp exon) of the NBF1 region. The point mutation was predicted to substitute a valine for the second glycine residue, G716V, of the Walker A motif of the NBF1 region, thereby altering a site that is conserved among all members of the ATP-binding-cassette superfamily. The mutation resulted in the loss of a BbvI restriction site allowing demonstration that the affected child was homozygous for the mutation, the parents heterozygous, and an unaffected sib homozygous for the wildtype allele. .0004 HYPER\ ``INSULIN``\ EMIC HYPOGLYCEMIA, FAMILIAL, 1 In 2 brothers with hyper\ ``INSULIN``\ emic hypoglycemia (256450), born of nonconsanguineous German parents, Thomas et al. (1996) identified compound heterozygosity for 2 mutations located in sequences predicted to affect RNA processing of the SUR transcript. The first mutation was a G-to-A transition located at the -1 residue, within the 3-prime splice site of the fifth exon (99-bp exon) of the NBF1 region. The transition destroyed a BstNI restriction site. A G-to-A mutation in the -1 invariant residue in the 3-prime splice site in other genes has been found to result in 100% skipping of the involved exon or in both exon skipping and cryptic 3-prime splice site activation. The second mutation was a branch point mutation (600509.0005) at nucleotide -20 of the 146-bp exon preceding the NBF1 encoding region. The presence of this point mutation disrupted an invariant A residue of the branch-point consensus. This A-to-G change resulted in the destruction of an engineered SpeI restriction endonuclease site. Restriction analysis demonstrated that the first mutant allele was of maternal origin and the second of paternal origin. An unaffected brother was homozygous for the wildtype alleles. .0005 HYPER\ ``INSULIN``\ EMIC HYPOGLYCEMIA, FAMILIAL, 1 See 600509.0004 and Thomas et al. (1996). .0006 HYPER\ ``INSULIN``\ EMIC HYPOGLYCEMIA, FAMILIAL, 1 In Ashkenazi Jewish families with hyper\ ``INSULIN``\ emic hypoglycemia (256450), Nestorowicz et al. (1996) identified a 3-bp deletion in exon 34 of the SUR gene, resulting in deletion of phenylalanine-1388. The deletion was associated with a specific haplotype (H1) in the D11S1901-D11S1310 region. The mutation led to the generation of a novel BseR1 restriction site. .0007 HYPER\ ``INSULIN``\ EMIC HYPOGLYCEMIA, FAMILIAL, 1 Dunne et al. (1997) identified a G-to-A transition in the terminal nucleotide of exon 35 of the SUR gene in homozygous state in a child from consanguineous Saudi Arabian parents. The child and 2 sibs had persistent hyper\ ``INSULIN``\ emic hypoglycemia of infancy (256450). The 2 affected sibs had undergone partial pancreatectomy for the disorder. The proband was born at term after a normal gestation, weighed 4.25 kg, and had macrosomia and plethora, features of in utero hyper\ ``INSULIN``\ ism. Two partial pancreatectomies were required for control of hypoglycemia. Histologic examination of the pancreas revealed diffuse nesidioblastosis. The parents were heterozygous for the G-A mutation. (The mutations previously discovered by Thomas et al. (1995), (1996) and by Nestorowicz et al. (1996) were not mentioned by Dunne et al. (1997).) .0008 HYPER\ ``INSULIN``\ EMIC HYPOGLYCEMIA, FAMILIAL, 1 In a sporadic case of persistent hyper\ ``INSULIN``\ emic hypoglycemia of infancy (256450) due to focal adenomatous hyperplasia, Verkarre et al. (1998) found a 4058G-C transversion in exon 33 of the paternally derived SUR gene, leading to an arg1353-to-pro (R1353P) amino acid substitution. The father was constitutionally heterozygous for the same mutation. This was 1 of 12 cases in which loss of maternal alleles of the 11p15 chromosomal region had been found, limited to the hyperplastic lesions of focal adenomatous hyperplasia. .0009 HYPER\ ``INSULIN``\ EMIC HYPOGLYCEMIA, FAMILIAL, 1 In a sporadic case of persistent hyper\ ``INSULIN``\ emic hypoglycemia of infancy (256450) due to focal adenomatous hyperplasia, Verkarre et al. (1998) found a 4261C-T transversion in exon 33 of the paternally derived SUR gene, leading to an arg1421-to-cys (R1421C) amino acid substitution. The father was constitutionally heterozygous for the same mutation. This was 1 of 12 cases in which loss of maternal alleles of the 11p15 chromosomal region had been found, limited to the hyperplastic lesions of focal adenomatous hyperplasia. Matsuo et al. (2000) analyzed the functional consequences of the R1421C mutation, which they referred to as R1420C. They showed that the mutation lowers the affinity of the nucleotide-binding fold 2 (NBF2) for ATP and ADP and abolishes the ability of nucleotide binding at NBF2 to stabilize 8-azido-ATP binding at NBF1. In addition, the mutation decreases the expression of potassium-ATP channels, and a smaller current in R1420C-PHHI beta cells leads to enhanced \ ``INSULIN``\ secretion. .0010 HYPER\ ``INSULIN``\ EMIC HYPOGLYCEMIA, FAMILIAL, 1 In 2 unrelated sporadic cases of persistent hyper\ ``INSULIN``\ emic hypoglycemia of infancy (256450) due to focal adenomatous hyperplasia, Verkarre et al. (1998) demonstrated loss of heterozygosity of the 11p15 region in the maternal allele and a point mutation in the paternally derived SUR allele: a 4480C-T transition in exon 37 leading to an arg1494-to-trp (R1494W) substitution. The father in each case was heterozygous for the R1494W mutation. .0011 HYPER\ ``INSULIN``\ EMIC HYPOGLYCEMIA, FAMILIAL, 1 In affected members of a Finnish family with hyper\ ``INSULIN``\ emic hypoglycemia (256450), Huopio et al. (2000) identified a heterozygous glu1506-to-lys (E1506K) mutation in the ABCC8 gene. This mutation led to a reduction, but not a complete loss, of K(ATP) channel activity. Huopio et al. (2003) characterized \ ``glucose``\ metabolism in adults heterozygous for this mutation. They found that the mutation results in congenital hyper\ ``INSULIN``\ ism in infancy, loss of \ ``INSULIN``\ secretory capacity in early adulthood, and \ ``diabetes``\ in middle age. Huopio et al. (2003) suggested that the disorder represents a new subtype of autosomal dominant \ ``diabetes``\ . They noted that, except for age at presentation, the E1506K mutation causes a disorder that fulfills the criteria for a form of MODY (see 606391). In a 6-year-old girl who was macrosomic at birth and had hyper\ ``INSULIN``\ emic hypoglycemia, Pinney et al. (2008) identified heterozygosity for what they designated the E1507K mutation in the ABCC8 gene. (Pinney et al., 2008 stated that they used numbering that included the alternatively spliced exon 17 sequence, and therefore the E1506K mutation reported by Huopio et al., 2000 is the same amino acid change as the E1507K mutation reported here.) Pinney et al. (2008) identified the E1507K in 8 other members of the family, none of whom had been suspected of having hypoglycemia, although 3 had severe symptoms, and 3 had mild symptoms consistent with hypoglycemia. The proband's mother and younger brother were the only mutation carriers who denied ever having symptoms of hypoglycemia. .0012 LEUCINE-SENSITIVE HYPOGLYCEMIA OF INFANCY In a 4-year-old boy with leucine-sensitive hypoglycemia (240800), Magge et al. (2004) identified a 4058G-A transition in exon 33 of the SUR1 gene that resulted in an arg1353-to-his (R1353H) substitution. Arg1353 of SUR1 is conserved across golden hamster, European hamster, rat, mouse, fruit fly, and cricket and is also conserved between human SUR1 and isoforms of SUR2 (601439). Rubidium ion efflux assay and electrophysiologic studies of R1353H SUR1 coexpressed with wildtype Kir6.2 (600937) in simian kidney fibroblasts demonstrated partially impaired ATP-dependent potassium channel function. .0013 HYPER\ ``INSULIN``\ EMIC HYPOGLYCEMIA, FAMILIAL, 1 In 15 of 24 Finnish patients with hyper\ ``INSULIN``\ emic hypoglycemia (256450), Otonkoski et al. (1999) identified homozygosity or heterozygosity for a 560T-A transversion in exon 4 of the ABCC8 gene, resulting in a val187-to-asp (V187D) substitution located toward the cytosolic end of the putative fourth or fifth transmembrane domain. In vitro studies demonstrated that the presence of the V187D mutation renders the potassium channel completely nonfunctional. Parents and sibs who were carriers of the mutation were apparently asymptomatic; Otonkoski et al. (1999) postulated the presence of another mutation in heterozygous affected individuals. .0014 HYPER\ ``INSULIN``\ EMIC HYPOGLYCEMIA, FAMILIAL, 1 In 5 affected members of the 3-generation family ('family 1') with hyper\ ``INSULIN``\ emic hypoglycemia (256450) originally reported by Thornton et al. (1998), Thornton et al. (2003) identified heterozygosity for a 3-bp deletion (4159-4161) in exon 34 of the ABCC8 gene, resulting in an in-frame deletion of a serine at codon 1387 (ser1387del). The mutation was not found in 4 unaffected family members. Studies in COSm6 cells revealed that potassium channels containing the mutation were not functional. Thornton et al. (2003) noted that this mutation is immediately adjacent to the F1388del ({60509.0006}) mutation that causes recessive hyper\ ``INSULIN``\ ism in Ashkenazi Jews. .0015 HYPER\ ``INSULIN``\ EMIC HYPOGLYCEMIA, FAMILIAL, 1 In an infant of Spanish descent diagnosed 3 days postnatally with hyper\ ``INSULIN``\ emic hypoglycemia (256450), Tornovsky et al. (2004) identified heterozygosity for a -64C-G transversion in the promoter of the ABCC8 gene on the paternal allele. Functional studies using a luciferase reporter vector revealed a 40% decrease in reporter gene expression for the mutant variant compared to wildtype, and the variant was not found in 100 control chromosomes tested. No mutation was found on the maternal allele. No focal lesion had been identified after near-total pancreatectomy, but the specimen was not available for reevaluation. .0016 \ ``diabetes``\ MELLITUS, PERMANENT NEONATAL, WITH NEUROLOGIC FEATURES In a 27-year-old man who had permanent neonatal \ ``diabetes``\ with severe developmental delay and generalized epileptiform activity on EEG (see 606176), Proks et al. (2006) identified heterozygosity for a de novo 394T-C transition in exon 3 of the ABCC8 gene, resulting in a phe132-to-leu (F132L) substitution. The mutation was not found in his unaffected parents or in 150 normal chromosomes. .0017 \ ``diabetes``\ MELLITUS, PERMANENT NEONATAL In a 5-year-old boy with permanent neonatal \ ``diabetes``\ mellitus (606176), Babenko et al. (2006) identified heterozygosity for a de novo leu213-to-arg (L213R) substitution. .0018 \ ``diabetes``\ MELLITUS, PERMANENT NEONATAL In a 17-year-old male with permanent neonatal \ ``diabetes``\ mellitus (606176), Babenko et al. (2006) identified heterozygosity for a de novo ile1424-to-val (I1424V) substitution. .0019 \ ``diabetes``\ MELLITUS, TRANSIENT NEONATAL, 2 In a 16-year-old French girl with transient neonatal \ ``diabetes``\ mellitus (610374) who had a recurrence of \ ``diabetes``\ at age 11 and in affected members of an unrelated 5-generation French family with transient neonatal \ ``diabetes``\ and adult-onset type II \ ``diabetes``\ mellitus (125853), Babenko et al. (2006) identified heterozygosity for an arg1379-to-cys (R1379C) substitution. The mutation arose de novo in the first patient. The 5-year-old female proband of the family had transient neonatal \ ``diabetes``\ . Her father developed \ ``diabetes``\ at age 32 that was treated with sulfonylureas, and her paternal grandmother was diagnosed with gestational \ ``diabetes``\ and treated with diet, and a paternal great-aunt was diagnosed at age 44 with \ ``diabetes``\ that was also treated with sulfonylureas. Babenko et al. (2006) proposed that mutations of the ABCC8 gene might give rise to a monogenic form of type II \ ``diabetes``\ with variable expression and age at onset. De Wet et al. (2007) performed functional studies of this mutation, which they designated R1380C, and demonstrated enhanced MgATP hydrolysis by purified isolated fusion proteins of maltose-binding protein and the second nucleotide-binding domain of ABCC8, in which the mutation is located. This increase in ATPase activity reduced the sensitivity of the channel to inhibition by MgATP and increased the whole-cell K(ATP) current. The authors noted that in pancreatic beta cells, such an increase in K(ATP) current would be expected to impair \ ``INSULIN``\ secretion and thereby cause \ ``diabetes``\ . .0020 \ ``diabetes``\ MELLITUS, TRANSIENT NEONATAL, 2 In a 2-year-old French boy with transient neonatal \ ``diabetes``\ mellitus (610374) and in affected members of an unrelated 3-generation French family with transient neonatal \ ``diabetes``\ and adult-onset type II \ ``diabetes``\ mellitus (125853), Babenko et al. (2006) identified heterozygosity for a leu583-to-val (L582V) substitution. The mutation arose de novo in the first patient. In the affected family, the 5-year-old male proband and his female cousin had transient neonatal \ ``diabetes``\ , whereas their mutation-positive fathers both developed after age 30 adult-onset type II \ ``diabetes``\ that was treated with diet alone; and their paternal grandfather also had type II \ ``diabetes``\ occurring later in life. Babenko et al. (2006) proposed that mutations of the ABCC8 gene might give rise to a monogenic form of type II \ ``diabetes``\ with variable expression and age at onset. .0021 \ ``diabetes``\ MELLITUS, PERMANENT NEONATAL In a patient from a cohort of 59 patients with permanent \ ``diabetes``\ (606176) who received a diagnosis before 6 months of age and who did not have a KCNJ11 mutation, Ellard et al. (2007) identified an 215A-G transition in the ABCC8 gene, resulting in an asn72-to-ser (N72S) substitution, in combination with mosaic segmental paternal isodisomy for 11pter to 11p14. This region includes the ABCC8 gene, and thus uniparental disomy had unmasked a recessively acting mutation. The father was heterozygous for the mutation but did not have \ ``diabetes``\ . .0022 \ ``diabetes``\ MELLITUS, PERMANENT NEONATAL In a patient with permanent neonatal \ ``diabetes``\ mellitus (606176), diagnosed before the age of 6 months, Ellard et al. (2007) identified a homozygous 1144G-A transition in the ABCC8 gene that resulted in a glu382-to-lys (E382K) substitution. The heterozygous, first-cousin parents were not diabetic. .0023 \ ``diabetes``\ MELLITUS, PERMANENT NEONATAL In a patient with permanent neonatal \ ``diabetes``\ mellitus (606176), diagnosed before the age of 6 months, the offspring of first cousins, Ellard et al. (2007) identified a homozygous mutation in the ABCC8 gene: a 3554C-A transversion resulting in an ala1185-to-glu substitution (A1185E). Neither parent was diabetic. .0024 \ ``diabetes``\ MELLITUS, PERMANENT NEONATAL In a patient with permanent neonatal \ ``diabetes``\ mellitus (606176), Ellard et al. (2007) observed compound heterozygosity for mutations in the ABCC8 gene. One allele carried a 134C-T transition resulting in a pro45-to-leu substitution (P45L); the other carried a 4201G-A transition resulting in a gly1401-to-arg substitution (G1401R; 600509.0025). .0025 \ ``diabetes``\ MELLITUS, PERMANENT NEONATAL See Ellard et al. (2007) and 600509.0024. .0026 \ ``diabetes``\ MELLITUS, PERMANENT NEONATAL In an infant with permanent neonatal \ ``diabetes``\ mellitus (606176) diagnosed at the age of 5 months, Ellard et al. (2007) found heterozygosity for a mutation in the ABCC8 gene: a 257T-G transversion resulting in a val86-to-gly substitution (V86G). This was one of 8 patients with this disorder associated with a heterozygous de novo mutation in ABCC8. .. _ABCC8 Phenotype: NCBI Phenotypes *************** * Gene Reviews * Persistent hyperinsulinemic hypoglycemia of infancy * \ ``Diabetes``\ mellitus type 2 * GTR * OMIM * Transient neonatal \ ``diabetes``\ mellitus 2 * Leucine-induced hypoglycemia * Permanent neonatal \ ``diabetes``\ mellitus .. _ABCC8 GO Term: Gene Ontology ************* * potassium ion transmembrane transporter activity * positive regulation of potassium ion transport * sulfonylurea receptor activity * ATPase activity, coupled to transmembrane movement of substances * response to lipopolysaccharide * response to \ ``insulin``\ stimulus * syntaxin binding * plasma membrane * voltage-gated potassium channel complex * response to pH * small molecule metabolic process * potassium channel activity * ATP binding * potassium ion transport * ion channel binding * regulation of \ ``insulin``\ secretion * energy reserve metabolic process * negative regulation of \ ``insulin``\ secretion * response to drug * potassium ion transmembrane transport * response to zinc ion * carbohydrate metabolic process * synaptic vesicle membrane * synaptic transmission * sarcolemma * transmembrane transport .. _ABCC8 Pathway: KEGG Pathways ************* * `ABC transporters `_ * `Type II \ ``diabetes``\ mellitus `_ .. _ABCC8 GeneRIF: GeneRIFs ******** * The R1380L & R1380C mutations in the ATP binding site enhance the off-rate of P(i), increasing MgATP hydrolysis, resulting in higher K(ATP) currents in pancreatic beta cells, thus reducing \ ``insulin``\ secretion and producing \ ``diabetes``\ . [`PMID 18025464`_] * The Kir6.2-W68R mutation causes a small reduction in ATP inhibition in the heterozygous state and an increase in the whole-cell ATP-sensitive potassium (KATP) current, explaining the phenotype of the patient. [`PMID 21540348`_] * An ABCC8/SUR1 mutation with relatively minor effects on K(ATP) channel activity and beta-cell \ ``glucose``\ sensing causes \ ``diabetes``\ in adulthood. [`PMID 18346985`_] * SUR1 is abundant in pancreatic endocrine granules, where its function remains to be established. [`PMID 17593344`_] * The clinical presentation of our two patients with a dominant ABCC8 mutation was milder than that of patients with the resessive form of the disease as they responded well to medical management. [`PMID 22308858`_] * the MDR-like core of SUR is linked with the K(IR) pore in KATP channels [`PMID 12213829`_] * Observational study of gene-environment interaction and pharmacogenomic / toxicogenomic. (HuGE Navigator) [`PMID 17118480`_] * The polymorphism of SUR1S1369A was associated with the therapeutic efficacy of gliclazide in type 2 \ ``diabetes``\ . After gliclazide treatment, there was association between T/G polymorphism and decrease of HbA1c. [`PMID 17118480`_] * Mutations of the same conserved glutamate residue in NBD2 of the sulfonylurea receptor 1 subunit of the KATP channel can result in either hyper\ ``insulin``\ ism or neonatal \ ``diabetes``\ . [`PMID 21617188`_] * ABCC8 mutations may have a role in Spanish patients with Hyper\ ``insulin``\ ism of Infancy [`PMID 16429405`_] * An amino acid substitution (L225P) causes permanent neonatal \ ``diabetes``\ but does not affect sulofonylurea sensitivity. [`PMID 17317760`_] * ATP regulates pancreatic beta-cell K(ATP) channel activity, not only by its direct actions on Kir6.2 pore subunit, but also via ATP modulation of Syn-1A binding to SUR1. [`PMID 21173146`_] * Mutations in ABCC8 and KCNJ11 are the most common causes of congenital hyper\ ``insulin``\ ism in Korean patients [`PMID 21422196`_] * Mutations in SUR1 are the cause of about 15% of Kir6.2 negative permanent neonatal \ ``diabetes``\ in Poland. [`PMID 19021632`_] * Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator) [`PMID 20682687`_] * results show SUR1 E208K and V324M mutations enhance transduction of Mg-nucleotide stimulation from SUR1 nucleotide binding folds to Kir6.2; suggest \ ``diabetes``\ severity determined by interplay between effects of a mutation on channel expression and gating [`PMID 20810569`_] * variant is not associated with type 2 \ ``diabetes``\ [`PMID 12540637`_] * Mutation carriers with neonatal \ ``diabetes``\ mellitus may be successflly transferred from \ ``insulin``\ to sulfonylurea agents. [`PMID 17213273`_] * Seven novel mutations were found in the ABCC8 coding region, one mutation was found in the KCNJ11 coding region, and one novel mutation was found in each of the two promoter regions screened. [`PMID 15579781`_] * A new TNDM mutation (R826W) in the first nucleotide-binding domain (NBD1) of SUR1, was identified. [`PMID 18497752`_] * Significant associations between eight SNPs, including the KCNJ11 E23K and ABCC8 S1369A variants, and T2D were found. [`PMID 17823772`_] * Data ound mutations in KCNJ11, INS and ABCC8 and GCK genes in permanent \ ``diabetes``\ mellitus with onset in the first 12 months of age. [`PMID 21544516`_] * Mutations can yield partially functioning channels, including cases of hyper\ ``insulin``\ ism that are fully responsive to diazoxide. therapy. [`PMID 15562009`_] * Alanine in HI: a silent mutation cries out! [`PMID 18290324`_] * SUR1 exon 16-3 cytosine/thymine polymorphism is a partial determinant of acute hyperglycaemia-cardiovascular risk factor in type 2 \ ``diabetes``\ [`PMID 17207885`_] * Kir6.2 and SUR1 co-localise with GLP-1 in L-cells and with \ ``glucose``\ dependent \ ``insulin``\ otropic peptide in K-cells in human ileum tissue [`PMID 17535866`_] * study identifies a group of congenital hyper\ ``insulin``\ ism-causing SUR1 mutations that cause channel biogenesis/trafficking defects [`PMID 17575084`_] * The role of Abcc8, which encodes sulfonylurea receptor 1 (SUR1), was assessed in progressive hemorrhagic necrosis. [`PMID 20410530`_] * Results demonstrate that some dominant mutations of SUR1 can cause diazoxide-unresponsive hyper\ ``insulin``\ ism. [`PMID 21536946`_] * Polymorphisms of SUR1 gene predicted conversion from impaired \ ``glucose``\ tolerance to type 2 \ ``diabetes``\ , and the effect of these polymorphisms on \ ``diabetes``\ risk was additive with E23K polymorphism of Kir6.2 gene. [`PMID 15579791`_] * Observational study of genotype prevalence. (HuGE Navigator) [`PMID 18162506`_] * study has shown that mutations in the KCNJ11 and ABCC8 are a major cause of transient neonatal \ ``diabetes``\ mellitus, accounting for 29% of all cases and 89% of non-6q24 transient neonatal \ ``diabetes``\ mellitus [`PMID 17446535`_] * ABCC8 mutation allele frequency in the Ashkenazi Jewish population and risk of focal hyper\ ``insulin``\ emic hypoglycemia [`PMID 21716120`_] * KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to susceptibility to type 2 diabeetes, \ ``glucose``\ intolerance and altered \ ``insulin``\ secretion in a Russian population. [`PMID 18758683`_] * Analysis of two KCNJ11 neonatal \ ``diabetes``\ mutations, V59G and V59A, and the analogous KCNJ8 I60G substitution: differences between the channel subtypes formed with SUR1. [`PMID 19139106`_] * Observational study and meta-analysis of gene-disease association. (HuGE Navigator) [`PMID 19498446`_] * Rare activating mutations cause neonatal \ ``diabetes``\ , whereas the common variants, E23K in KCNJ11 and S1369A in ABCC8, are in strong linkage disequilibrium, constituting a haplotype that predisposes to type 2 \ ``diabetes``\ [`PMID 19587354`_] * \ ``Insulin``\ secretagogues promote \ ``Insulin``\ release by binding to sulfonylurea receptors on pancreatic beta-cells (SUR1). However, these drugs also bind to receptor isoforms on cardiac myocytes (SUR2A) and vascular smooth muscle (SUR2B). [`PMID 21923736`_] * Conserved intramolecular disulfide bond is critical to trafficking and fate of ATP-binding cassette (ABC) transporters ABCB6 and sulfonylurea receptor 1 (SUR1)/ABCC8. [`PMID 21199866`_] * Genetic mechanism to explain atypical histological diffuse forms of congenital hyper\ ``insulin``\ ism due to mutations of ABCC8. [`PMID 17942822`_] * Paternal isodisomy of chromosome 11 unmasks a recessively acting gain-of-function mutation in the ABCC8 gene and causes deregulation of imprinted genes and development of neonatal \ ``diabetes``\ and hemihypertrophy. [`PMID 17942821`_] * K(IR)6.2-based channels with diabetogenic receptors reveal that MgATP-dependent hyper-stimulation of mutant SUR can compromise the ability of K(ATP) channels to function as metabolic sensors [`PMID 18281290`_] * Affinity Capture-Western [`PMID 12941953`_] * Observational study of gene-disease association. (HuGE Navigator) [`PMID 20863361`_] * The phenotype associated with dominant ABCC8/KCNJ11 mutations ranges from asymptomatic macrosomia to persistent hyper\ ``insulin``\ aemic hypoglycaemia in childhood. [`PMID 21674179`_] * Data show that ABCC8 or KCNJ11 defects were found in 82% of the CHI cases. [`PMID 20685672`_] * Nonsense mutation and a missense mutation in ABCC8 gene is associated with aberrant pancreatic development in congenital hyper\ ``insulin``\ ism. [`PMID 18988933`_] * Messenger ribonucleic acid quantification of ABC transporters revealed alterations in ABC transporter expression in failing human hearts compared to nonfailing controls. These include increased expression of K(ATP) channel regulatory subunits ABCC8 [`PMID 18392808`_] * SUR1 mutations constitute a new genetic aetiology for neonatal \ ``diabetes``\ and they act by reducing the K(ATP) channel's ATP sensitivity [`PMID 16613899`_] * Mutations in the K(ATP) channel which result in permanent neonatal \ ``diabetes``\ . [`PMID 20922570`_] * Data suggest that the SUR1-regulated NCCa-ATP channel may be associated with germinal matrix hemorrhage (GMH), and that pharmacological block of these channels could potentially reduce the incidence of GMH. [`PMID 18679166`_] * study describes a unique, maternally inherited dominant-negative mutation in ABCC8 that causes congenital hyper\ ``insulin``\ ism in some but not all family members carrying the mutation; differences in transcript expression may determine the clinical phenotype [`PMID 22106158`_] * Data observed that ABCC8 as well as the interaction between PPARG and HNF4A may contribute to post-challenge \ ``insulin``\ secretion. [`PMID 20079163`_] * Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator) [`PMID 20079163`_] * inc activates KATP by binding itself to extracellular His-326 and His-332 of the SUR1 subunit. [`PMID 15613469`_] * Recessive inactivating mutations in ABCC8 and KCNJ11 are the most common cause of CHI. [`PMID 19254908`_] * Three novel heterozygous ATP-binding cassette sub-family C member 8 mis-sense mutations (G1485E, D1506E and M1514K) were identified in 4 cases of hyper\ ``insulin``\ aemic hypoglycaemia [`PMID 20573158`_] * study shows a diabetogenic mutation in an unexplored helix preceding the ABC core of SUR1 increases open probability of (SUR1/Kir6.2)(4) channel (KATP) by changing rates of transitions to and from the long-lived, inhibitory ligand-stabilized closed state [`PMID 22020219`_] * Assembly limits the pharmacological complexity of ATP-sensitive potassium channels [`PMID 11825905`_] * Dominant mutations in ABCC8 accounted for 12 percent of cases of neonatal \ ``diabetes``\ in the study group. \ ``diabetes``\ results when stimulatory action of SUR1 on Kir pore is elevated. [`PMID 16885549`_] * analysis of mutations in Kir6.2 (KCNJ11) and SUR1 (ABCC8), the spectrum of phenotypes, and the implications for treatment when patients are diagnosed with mutations in these genes [review] [`PMID 16416420`_] * Novel mutations in ABCC8 are found in 32% of children with congenital hyper\ ``insulin``\ ism. [`PMID 21378087`_] * the minimum birth prevalence of ABCC8-congenital hyper\ ``insulin``\ ism of infancy in Norway to 1:70,000 during the past decade [`PMID 19475716`_] * This new ABCC8 mutation is associated with neonatal hyper\ ``insulin``\ ism progressing within 10 years to \ ``insulin``\ openic \ ``diabetes``\ . [`PMID 18390792`_] * the dominant heterozygous germ line E1506K mutation in ABCC8 associated with persistent hypoglycemia in the newborn period and \ ``diabetes``\ in adulthood [`PMID 20042013`_] * MRP8/MRP14 complex inhibited proliferation and differentiation of myoblasts and induced apoptosis via activation of caspase-3 in a time- and dose-dependent manner. Activated macrophages can destroy and regenerate myocytes via MRP8/MRP14. [`PMID 12937135`_] * Mutation analysis showed that the child with congential hyper\ ``insulin``\ ism has a compound heterozygote for two missense mutations in the ABCC8 gene. [`PMID 21992908`_] * ABCC8 (SUR1) and KCNJ11 (KIR6.2) mutations in persistent hyper\ ``insulin``\ emic hypoglycemia of infancy and evaluation of different therapeutic measures. Not predictive of response to drugs. [`PMID 12199344`_] * In two ohorts of Chinese type 2 diabetic patients, there us consistent evidence that the Ser1369Ala variant in the ABCC8 gene can influence the antidiabetic efficacy of gliclazide. [`PMID 18599530`_] * down-regulation of this channel may facilitate myometrial function during late pregnancy [`PMID 12356945`_] * Alleles c of SUR1 are significantly increase the susceptibility to gestational \ ``diabetes``\ mellitus. [`PMID 15840308`_] * Oral sulfonylurea therapy is safe and effective in the short term in most patients with \ ``diabetes``\ due to SUR1 mutations and may successfully replace treatment with \ ``insulin``\ injections. [`PMID 18025408`_] * allelic variation in exon 18, \ ``insulin``\ secretion and \ ``insulin``\ sensitivity in nondiabetic relatives of type 2 diabetic subjects [`PMID 12149601`_] * SUR-1 exon 16 and exon 31 polymorphisms are significantly associated with HbA1c concentration. [`PMID 19766903`_] * homozygotes of the ABCC8 exon16-3T/C variant responded better to repaglinide in \ ``insulin``\ sensitivity than the T/C and T/T genotype [`PMID 18664331`_] * This is the first report of a patient with clinically severe autosomal-recessive diffuse CHI due to a compound heterozygous ABCC8 mutation that has resulted in spontaneous resolution at such an early age. [`PMID 20215776`_] * sequential activation of two transcription factors, HIF and Sp1, is required to stimulate transcription of Abcc8 following cerebral ischemia. [`PMID 22086197`_] * Long-term follow-up of three patients with persistent hyper\ ``insulin``\ emic hypoglycemia of infancy due to mutations in the ABCC8 gene. [`PMID 18339976`_] * We identified spliced form of human sulfonylurea receptor (SUR)1 mRNA lacking exon 2 (SUR1D2) and resulting in a frame shift and an immediate stop codon in exon 3 leading to translation of a 5.6-kDa prodiabetic peptide. [`PMID 21671119`_] * Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) [`PMID 20628086`_] * Meta-analysis of gene-disease association. (HuGE Navigator) [`PMID 15842514`_] * Identification of a familial hyper\ ``insulin``\ ism-causing mutation in the sulfonylurea receptor 1 that prevents normal trafficking and function of KATP channels. [`PMID 11867634`_] * The mutation of ABCC8 is recessively inherited. [`PMID 18596924`_] * In conjunction with this PIP2-dependent process, SUR1 also regulates channel activity via a PIP2-independent, but MgADP-dependent process. [`PMID 16373383`_] * Two cases of adult diabetic patients-considered and treated as \ ``insulin``\ -dependent diabetic patients since adolescence-who, in fact, turned out to be heterozygous for an ABCC8 mutation. [`PMID 19342262`_] * Six new heterozygous ABCC8 mutations, mainly in patients presenting the transient form of neonatal \ ``diabetes``\ . [`PMID 17389331`_] * a novel ABCC8 V84I mutation, which segregated with autosomal dominant transmission of mild hyperglycemia within three generations [`PMID 21214702`_] * SUR1/Kir6.2 gene region contributes to risk of type 2 \ ``diabetes``\ and encodes targets for hypoglycemic medications. Link between mechanism of disease and targets for pharmacological treatment. [`PMID 15111507`_] * We present a term large-for-gestation neonate with congenital hyper\ ``insulin``\ ism, who was found to have a novel sporadic missense mutation in the ABCC8 gene [`PMID 17597441`_] * Mutations of the gene in \ ``diabetes``\ mellitus and hyper\ ``insulin``\ ism (Review) [`PMID 18767144`_] * genetic association studies in United Kingdom: Data suggest that ABCC8 mutations is the cause of maturity-onset \ ``diabetes``\ mellitus in some patients. [`PMID 21989597`_] * ABCC8 mutations cause PNDM, TNDM or permanent \ ``diabetes``\ diagnosed outside the neonatal period. [`PMID 17919176`_] * The A1369 variant increases K(ATP) channel MgATPase activity, providing a plausible molecular mechanism by which the K23/A1369 haplotype increases susceptibility to T2D in humans homozygous for these variants. [`PMID 22187380`_] * There is no association between the ABCC8 polymorphism gene and the beta-cell function or the prevalence of chronic diabetic complications in obese patients with long-term T2DM, except for brain stroke. [`PMID 17516295`_] * implications of SUR1 in the genetic and pathopysiological mechanisms of type 2 \ ``diabetes``\ mellitus [`PMID 11938023`_] * Affinity Capture-Western [`PMID 14660679`_] .. _PMID 18025464: http://www.ncbi.nlm.nih.gov/pubmed/18025464 .. _PMID 21540348: http://www.ncbi.nlm.nih.gov/pubmed/21540348 .. _PMID 18346985: http://www.ncbi.nlm.nih.gov/pubmed/18346985 .. _PMID 17593344: http://www.ncbi.nlm.nih.gov/pubmed/17593344 .. _PMID 22308858: http://www.ncbi.nlm.nih.gov/pubmed/22308858 .. _PMID 12213829: http://www.ncbi.nlm.nih.gov/pubmed/12213829 .. _PMID 17118480: http://www.ncbi.nlm.nih.gov/pubmed/17118480 .. _PMID 21617188: http://www.ncbi.nlm.nih.gov/pubmed/21617188 .. _PMID 16429405: http://www.ncbi.nlm.nih.gov/pubmed/16429405 .. _PMID 17317760: http://www.ncbi.nlm.nih.gov/pubmed/17317760 .. _PMID 21173146: http://www.ncbi.nlm.nih.gov/pubmed/21173146 .. _PMID 21422196: http://www.ncbi.nlm.nih.gov/pubmed/21422196 .. _PMID 19021632: http://www.ncbi.nlm.nih.gov/pubmed/19021632 .. _PMID 20682687: http://www.ncbi.nlm.nih.gov/pubmed/20682687 .. _PMID 20810569: http://www.ncbi.nlm.nih.gov/pubmed/20810569 .. _PMID 12540637: http://www.ncbi.nlm.nih.gov/pubmed/12540637 .. _PMID 17213273: http://www.ncbi.nlm.nih.gov/pubmed/17213273 .. _PMID 15579781: http://www.ncbi.nlm.nih.gov/pubmed/15579781 .. _PMID 18497752: http://www.ncbi.nlm.nih.gov/pubmed/18497752 .. _PMID 17823772: http://www.ncbi.nlm.nih.gov/pubmed/17823772 .. _PMID 21544516: http://www.ncbi.nlm.nih.gov/pubmed/21544516 .. _PMID 15562009: http://www.ncbi.nlm.nih.gov/pubmed/15562009 .. _PMID 18290324: http://www.ncbi.nlm.nih.gov/pubmed/18290324 .. _PMID 17207885: http://www.ncbi.nlm.nih.gov/pubmed/17207885 .. _PMID 17535866: http://www.ncbi.nlm.nih.gov/pubmed/17535866 .. _PMID 17575084: http://www.ncbi.nlm.nih.gov/pubmed/17575084 .. _PMID 20410530: http://www.ncbi.nlm.nih.gov/pubmed/20410530 .. _PMID 21536946: http://www.ncbi.nlm.nih.gov/pubmed/21536946 .. _PMID 15579791: http://www.ncbi.nlm.nih.gov/pubmed/15579791 .. _PMID 18162506: http://www.ncbi.nlm.nih.gov/pubmed/18162506 .. _PMID 17446535: http://www.ncbi.nlm.nih.gov/pubmed/17446535 .. _PMID 21716120: http://www.ncbi.nlm.nih.gov/pubmed/21716120 .. _PMID 18758683: http://www.ncbi.nlm.nih.gov/pubmed/18758683 .. _PMID 19139106: http://www.ncbi.nlm.nih.gov/pubmed/19139106 .. _PMID 19498446: http://www.ncbi.nlm.nih.gov/pubmed/19498446 .. _PMID 19587354: http://www.ncbi.nlm.nih.gov/pubmed/19587354 .. _PMID 21923736: http://www.ncbi.nlm.nih.gov/pubmed/21923736 .. _PMID 21199866: http://www.ncbi.nlm.nih.gov/pubmed/21199866 .. _PMID 17942822: http://www.ncbi.nlm.nih.gov/pubmed/17942822 .. _PMID 17942821: http://www.ncbi.nlm.nih.gov/pubmed/17942821 .. _PMID 18281290: http://www.ncbi.nlm.nih.gov/pubmed/18281290 .. _PMID 12941953: http://www.ncbi.nlm.nih.gov/pubmed/12941953 .. _PMID 20863361: http://www.ncbi.nlm.nih.gov/pubmed/20863361 .. _PMID 21674179: http://www.ncbi.nlm.nih.gov/pubmed/21674179 .. _PMID 20685672: http://www.ncbi.nlm.nih.gov/pubmed/20685672 .. _PMID 18988933: http://www.ncbi.nlm.nih.gov/pubmed/18988933 .. _PMID 18392808: http://www.ncbi.nlm.nih.gov/pubmed/18392808 .. _PMID 16613899: http://www.ncbi.nlm.nih.gov/pubmed/16613899 .. _PMID 20922570: http://www.ncbi.nlm.nih.gov/pubmed/20922570 .. _PMID 18679166: http://www.ncbi.nlm.nih.gov/pubmed/18679166 .. _PMID 22106158: http://www.ncbi.nlm.nih.gov/pubmed/22106158 .. _PMID 20079163: http://www.ncbi.nlm.nih.gov/pubmed/20079163 .. _PMID 15613469: http://www.ncbi.nlm.nih.gov/pubmed/15613469 .. _PMID 19254908: http://www.ncbi.nlm.nih.gov/pubmed/19254908 .. _PMID 20573158: http://www.ncbi.nlm.nih.gov/pubmed/20573158 .. _PMID 22020219: http://www.ncbi.nlm.nih.gov/pubmed/22020219 .. _PMID 11825905: http://www.ncbi.nlm.nih.gov/pubmed/11825905 .. _PMID 16885549: http://www.ncbi.nlm.nih.gov/pubmed/16885549 .. _PMID 16416420: http://www.ncbi.nlm.nih.gov/pubmed/16416420 .. _PMID 21378087: http://www.ncbi.nlm.nih.gov/pubmed/21378087 .. _PMID 19475716: http://www.ncbi.nlm.nih.gov/pubmed/19475716 .. _PMID 18390792: http://www.ncbi.nlm.nih.gov/pubmed/18390792 .. _PMID 20042013: http://www.ncbi.nlm.nih.gov/pubmed/20042013 .. _PMID 12937135: http://www.ncbi.nlm.nih.gov/pubmed/12937135 .. _PMID 21992908: http://www.ncbi.nlm.nih.gov/pubmed/21992908 .. _PMID 12199344: http://www.ncbi.nlm.nih.gov/pubmed/12199344 .. _PMID 18599530: http://www.ncbi.nlm.nih.gov/pubmed/18599530 .. _PMID 12356945: http://www.ncbi.nlm.nih.gov/pubmed/12356945 .. _PMID 15840308: http://www.ncbi.nlm.nih.gov/pubmed/15840308 .. _PMID 18025408: http://www.ncbi.nlm.nih.gov/pubmed/18025408 .. _PMID 12149601: http://www.ncbi.nlm.nih.gov/pubmed/12149601 .. _PMID 19766903: http://www.ncbi.nlm.nih.gov/pubmed/19766903 .. _PMID 18664331: http://www.ncbi.nlm.nih.gov/pubmed/18664331 .. _PMID 20215776: http://www.ncbi.nlm.nih.gov/pubmed/20215776 .. _PMID 22086197: http://www.ncbi.nlm.nih.gov/pubmed/22086197 .. _PMID 18339976: http://www.ncbi.nlm.nih.gov/pubmed/18339976 .. _PMID 21671119: http://www.ncbi.nlm.nih.gov/pubmed/21671119 .. _PMID 20628086: http://www.ncbi.nlm.nih.gov/pubmed/20628086 .. _PMID 15842514: http://www.ncbi.nlm.nih.gov/pubmed/15842514 .. _PMID 11867634: http://www.ncbi.nlm.nih.gov/pubmed/11867634 .. _PMID 18596924: http://www.ncbi.nlm.nih.gov/pubmed/18596924 .. _PMID 16373383: http://www.ncbi.nlm.nih.gov/pubmed/16373383 .. _PMID 19342262: http://www.ncbi.nlm.nih.gov/pubmed/19342262 .. _PMID 17389331: http://www.ncbi.nlm.nih.gov/pubmed/17389331 .. _PMID 21214702: http://www.ncbi.nlm.nih.gov/pubmed/21214702 .. _PMID 15111507: http://www.ncbi.nlm.nih.gov/pubmed/15111507 .. _PMID 17597441: http://www.ncbi.nlm.nih.gov/pubmed/17597441 .. _PMID 18767144: http://www.ncbi.nlm.nih.gov/pubmed/18767144 .. _PMID 21989597: http://www.ncbi.nlm.nih.gov/pubmed/21989597 .. _PMID 17919176: http://www.ncbi.nlm.nih.gov/pubmed/17919176 .. _PMID 22187380: http://www.ncbi.nlm.nih.gov/pubmed/22187380 .. _PMID 17516295: http://www.ncbi.nlm.nih.gov/pubmed/17516295 .. _PMID 11938023: http://www.ncbi.nlm.nih.gov/pubmed/11938023 .. _PMID 14660679: http://www.ncbi.nlm.nih.gov/pubmed/14660679 .. _ABCC8 Pubmed: PubMed Articles *************** *Recent articles:* * Woo SK et al. "Sequential activation of hypoxia-inducible factor 1 and specificity protein 1 is required for hypoxia-induced transcriptional stimulation of Abcc8." J Cereb Blood Flow Metab. 2012 Mar;32(3):525-36. `PMID 22086197`_ * Oçal G et al. "Clinical characteristics of recessive and dominant congenital hyperinsulinism due to mutation(s) in the ABCC8/KCNJ11 genes encoding the ATP-sensitive potasium channel in the pancreatic beta cell." J Pediatr Endocrinol Metab. 2011;24(11-12):1019-23. `PMID 22308858`_ * Abdelmoneim AS et al. "Variations in tissue selectivity amongst insulin secretagogues: a systematic review." Diabetes Obes Metab. 2012 Feb;14(2):130-8. `PMID 21923736`_ * Shemer R et al. "Relative expression of a dominant mutated ABCC8 allele determines the clinical manifestation of congenital hyperinsulinism." Diabetes. 2012 Jan;61(1):258-63. `PMID 22106158`_ * Bowman P et al. "Heterozygous ABCC8 mutations are a cause of MODY." Diabetologia. 2012 Jan;55(1):123-7. `PMID 21989597`_ * Fatehi M et al. "The ATP-sensitive K(+) channel ABCC8 S1369A type 2 diabetes risk variant increases MgATPase activity." Diabetes. 2012 Jan;61(1):241-9. `PMID 22187380`_ * Babenko AP et al. "Mechanism of KATP hyperactivity and sulfonylurea tolerance due to a diabetogenic mutation in L0 helix of sulfonylurea receptor 1 (ABCC8)." FEBS Lett. 2011 Nov 16;585(22):3555-9. `PMID 22020219`_ * Glaser B et al. "ABCC8 mutation allele frequency in the Ashkenazi Jewish population and risk of focal hyperinsulinemic hypoglycemia." Genet Med. 2011 Oct;13(10):891-4. `PMID 21716120`_ * Kapoor RR et al. "Hyperinsulinaemic hypoglycaemia and diabetes mellitus due to dominant ABCC8/KCNJ11 mutations." Diabetologia. 2011 Oct;54(10):2575-83. `PMID 21674179`_ * Thakur S et al. "Congenital hyperinsulinism caused by mutations in ABCC8 (SUR1) gene." Indian Pediatr. 2011 Sep;48(9):733-4. `PMID 21992908`_ .. _PMID 21923736: http://www.ncbi.nlm.nih.gov/pubmed/21923736 .. _PMID 21716120: http://www.ncbi.nlm.nih.gov/pubmed/21716120 .. _PMID 21992908: http://www.ncbi.nlm.nih.gov/pubmed/21992908 .. _PMID 22106158: http://www.ncbi.nlm.nih.gov/pubmed/22106158 .. _PMID 21989597: http://www.ncbi.nlm.nih.gov/pubmed/21989597 .. _PMID 21674179: http://www.ncbi.nlm.nih.gov/pubmed/21674179 .. _PMID 22187380: http://www.ncbi.nlm.nih.gov/pubmed/22187380 .. _PMID 22020219: http://www.ncbi.nlm.nih.gov/pubmed/22020219 .. _PMID 22086197: http://www.ncbi.nlm.nih.gov/pubmed/22086197 .. _PMID 22308858: http://www.ncbi.nlm.nih.gov/pubmed/22308858 *Top Pubmed articles linked to gene ABCC8 matching any search term:* * Habeb AM et al. "Permanent neonatal diabetes: different aetiology in Arabs compared to Europeans." Arch Dis Child. 2012 Aug;97(8):721-3. `PMID 22859427`_ * Oztekin O et al. "Successful sulfonylurea treatment of a neonate with neonatal diabetes mellitus due to a novel missense mutation, p.P1199L, in the ABCC8 gene." J Perinatol. 2012 Aug;32(8):645-7. `PMID 22842804`_ * Jahnavi S et al. "Clinical and molecular characterization of neonatal diabetes and monogenic syndromic diabetes in Asian Indian children." Clin Genet. 2012 Jul 25;. `PMID 22831748`_ * Shah B et al. "Improved long-term glucose control in neonatal diabetes mellitus after early sulfonylurea allergy." J Pediatr Endocrinol Metab. 2012;25(3-4):353-6. `PMID 22768668`_ * Ooi HL et al. "Three cases of permanent neonatal diabetes mellitus: genotypes and management outcome." Singapore Med J. 2012 Jul;53(7):e142-4. `PMID 22815030`_ * Bonnefond A et al. "Whole-Exome Sequencing and High Throughput Genotyping Identified KCNJ11 as the Thirteenth MODY Gene." PLoS One. 2012;7(6):e37423. `PMID 22701567`_ * Jain V et al. "Permanent neonatal diabetes caused by a novel mutation." Indian Pediatr. 2012 Jun 8;49(6):486-8. `PMID 22796691`_ * Aydin BK et al. "Permanent neonatal diabetes mellitus: same mutation, different glycemic control with sulfonylurea therapy on long-term follow-up." J Clin Res Pediatr Endocrinol. 2012 Jun;4(2):107-10. `PMID 22672870`_ * Johansson S et al. "Exome sequencing and genetic testing for MODY." PLoS One. 2012;7(5):e38050. `PMID 22662265`_ * Gonen MS et al. "Effects of Single Nucleotide Polymorphisms in K(ATP) Channel Genes on Type 2 Diabetes in a Turkish Population." Arch Med Res. 2012 May;43(4):317-23. `PMID 22704848`_ * Oçal G et al. "Clinical characteristics of recessive and dominant congenital hyperinsulinism due to mutation(s) in the ABCC8/KCNJ11 genes encoding the ATP-sensitive potasium channel in the pancreatic beta cell." J Pediatr Endocrinol Metab. 2011;24(11-12):1019-23. `PMID 22308858`_ * Kapoor RR et al. "Hyperinsulinaemic hypoglycaemia and diabetes mellitus due to dominant ABCC8/KCNJ11 mutations." Diabetologia. 2011 Oct;54(10):2575-83. `PMID 21674179`_ * Männikkö R et al. "A conserved tryptophan at the membrane-water interface acts as a gatekeeper for Kir6.2/SUR1 channels and causes neonatal diabetes when mutated." J Physiol. 2011 Jul 1;589(Pt 13):3071-83. `PMID 21540348`_ * Bellanné-Chantelot C et al. "ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism." J Med Genet. 2010 Nov;47(11):752-9. `PMID 20685672`_ * Nikolac N et al. "Metabolic control in type 2 diabetes is associated with sulfonylurea receptor-1 (SUR-1) but not with KCNJ11 polymorphisms." Arch Med Res. 2009 Jul;40(5):387-92. `PMID 19766903`_ * Feng Y et al. "Ser1369Ala variant in sulfonylurea receptor gene ABCC8 is associated with antidiabetic efficacy of gliclazide in Chinese type 2 diabetic patients." Diabetes Care. 2008 Oct;31(10):1939-44. `PMID 18599530`_ * He YY et al. "Association of KCNJ11 and ABCC8 genetic polymorphisms with response to repaglinide in Chinese diabetic patients." Acta Pharmacol Sin. 2008 Aug;29(8):983-9. `PMID 18664331`_ * Rafiq M et al. "Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations." Diabetes Care. 2008 Feb;31(2):204-9. `PMID 18025408`_ * Nielsen LB et al. "Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes." Eur J Endocrinol. 2007 Jun;156(6):663-71. `PMID 17535866`_ * Vaxillaire M et al. "New ABCC8 mutations in relapsing neonatal diabetes and clinical features." Diabetes. 2007 Jun;56(6):1737-41. `PMID 17389331`_ .. _PMID 22701567: http://www.ncbi.nlm.nih.gov/pubmed/22701567 .. _PMID 21540348: http://www.ncbi.nlm.nih.gov/pubmed/21540348 .. _PMID 18025408: http://www.ncbi.nlm.nih.gov/pubmed/18025408 .. _PMID 22831748: http://www.ncbi.nlm.nih.gov/pubmed/22831748 .. _PMID 20685672: http://www.ncbi.nlm.nih.gov/pubmed/20685672 .. _PMID 17535866: http://www.ncbi.nlm.nih.gov/pubmed/17535866 .. _PMID 22815030: http://www.ncbi.nlm.nih.gov/pubmed/22815030 .. _PMID 19766903: http://www.ncbi.nlm.nih.gov/pubmed/19766903 .. _PMID 22672870: http://www.ncbi.nlm.nih.gov/pubmed/22672870 .. _PMID 21674179: http://www.ncbi.nlm.nih.gov/pubmed/21674179 .. _PMID 18664331: http://www.ncbi.nlm.nih.gov/pubmed/18664331 .. _PMID 22796691: http://www.ncbi.nlm.nih.gov/pubmed/22796691 .. _PMID 22859427: http://www.ncbi.nlm.nih.gov/pubmed/22859427 .. _PMID 17389331: http://www.ncbi.nlm.nih.gov/pubmed/17389331 .. _PMID 18599530: http://www.ncbi.nlm.nih.gov/pubmed/18599530 .. _PMID 22662265: http://www.ncbi.nlm.nih.gov/pubmed/22662265 .. _PMID 22704848: http://www.ncbi.nlm.nih.gov/pubmed/22704848 .. _PMID 22842804: http://www.ncbi.nlm.nih.gov/pubmed/22842804 .. _PMID 22308858: http://www.ncbi.nlm.nih.gov/pubmed/22308858 .. _PMID 22768668: http://www.ncbi.nlm.nih.gov/pubmed/22768668