ABCMdb

ABCC8 p.Arg1379Cys

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Publications

PMID: 19095654 [PubMed] Ackermann S et al: "17beta-Estradiol modulates apoptosis in pancreatic beta-cells by specific involvement of the sulfonylurea receptor (SUR) isoform SUR1."

No. Sentence Comment

9 SUR1-specific 17beta-estradiol-induced apoptosis was either abolished by the mutation M1289T in transmembrane helix 17 of SUR1 or clearly enhanced by two mutations in nucleotide binding fold 2 (R1379C, R1379L). Login to comment
43 In addition, we explored in which manner the action of 17beta-estradiol was influenced by mutations (M1289T, R1379C, R1379L) in the SUR1 gene (ABCC8) that are of special importance for SUR function (18-20). Login to comment
46 EXPERIMENTAL PROCEDURES Mutagenesis, Transfection, and Cell Culture-HEK293 cells (German Collection of Microorganisms and Cell Cultures, DSMZ, Braunschweig, Germany) were stably transfected with pcDNA3.1 expression vector (Invitrogen) containing the coding sequence of rat SUR1 (GenBankTM accession number X97279), SUR1(M1289T), SUR1(R1379C), SUR1(R1379L), murine SUR2A (GenBank D86037), SUR2A(Y1206S), murine SUR2B (GenBank D86038), or SUR2B(Y1206S), or they were transfected with empty pcDNA3.1 expression vector (Invitrogen). Login to comment
105 By contrast, apoptosis in cells expressing mutants SUR1(R1379C) or SUR1(R1379L) was potentiated to a large extent (Figs. Login to comment
120 After treatment of SUR1-, SUR1(M1289T)-, SUR2A-, and SUR2B-expressing HEK293 cells (A and B) or of SUR1, SUR1(R1379C), and SUR1(R1379L) cells (C) with 17beta-estradiol (100 ␮mol/liter, 24 h), cell detachmentorchangesinnuclearmorphologyweredeterminedandcomparedwiththeresultsobtainedwith pcDNA control cells (please note the different scales in A and C). Login to comment
145 HEK293 cells stably expressing SUR1, SUR1(M1289T), SUR1(R1379C), or pcDNA control cells (A) were compared with cells from the clonal beta-cell lines HIT-T15 and RIN-m5F (B) or to isolated islets from SUR1-expressing wild type mice (SUR1wt) or SUR1KO mice (C) after treatment with 100 ␮mol/liter 17beta-estradiol (E2) or solvent (solv.) Login to comment
184 This SUR1-dependent effect of 17beta-estradiol is either abolished by mutation M1289T or enhanced by mutations R1379C or R1379L in SUR1. Login to comment
225 The mutation M1289T completely abolishes the SUR1-specific apoptotic effects of KATP channel blockers glibenclamide (3) or resveratrol (4), or 17beta-estradiol obviously without directly affecting binding of these substances to SUR1. Login to comment
227 To see whether SUR1-mediated apoptosis is linked with ATP hydrolysis, we explored the effects of mutations R1379C and R1379L in nucleotide binding fold 2 of SUR1 on 17beta-estradiol action. Login to comment
44 In addition, we explored in which manner the action of 17beta-estradiol was influenced by mutations (M1289T, R1379C, R1379L) in the SUR1 gene (ABCC8) that are of special importance for SUR function (18-20). Login to comment
47 EXPERIMENTAL PROCEDURES Mutagenesis, Transfection, and Cell Culture-HEK293 cells (German Collection of Microorganisms and Cell Cultures, DSMZ, Braunschweig, Germany) were stably transfected with pcDNA3.1 expression vector (Invitrogen) containing the coding sequence of rat SUR1 (GenBankTM accession number X97279), SUR1(M1289T), SUR1(R1379C), SUR1(R1379L), murine SUR2A (GenBank D86037), SUR2A(Y1206S), murine SUR2B (GenBank D86038), or SUR2B(Y1206S), or they were transfected with empty pcDNA3.1 expression vector (Invitrogen). Login to comment
104 By contrast, apoptosis in cells expressing mutants SUR1(R1379C) or SUR1(R1379L) was potentiated to a large extent (Figs. 3C and 4A): compared with SUR1, cell detachment was increased by a factor of 3.0 or 2.7, respectively, and the rate of apoptotic nuclei was elevated b07;3-fold. Login to comment
118 After treatment of SUR1-, SUR1(M1289T)-, SUR2A-, and SUR2B-expressing HEK293 cells (A and B) or of SUR1, SUR1(R1379C), and SUR1(R1379L) cells (C) with 17beta-estradiol (100 òe;mol/liter, 24 h), cell detachmentorchangesinnuclearmorphologyweredeterminedandcomparedwiththeresultsobtainedwith pcDNA control cells (please note the different scales in A and C). Login to comment
143 HEK293 cells stably expressing SUR1, SUR1(M1289T), SUR1(R1379C), or pcDNA control cells (A) were compared with cells from the clonal beta-cell lines HIT-T15 and RIN-m5F (B) or to isolated islets from SUR1-expressing wild type mice (SUR1wt) or SUR1KO mice (C) after treatment with 100 òe;mol/liter 17beta-estradiol (E2) or solvent (solv.) Login to comment
182 This SUR1-dependent effect of 17beta-estradiol is either abolished by mutation M1289T or enhanced by mutations R1379C or R1379L in SUR1. Login to comment
106 By contrast, apoptosis in cells expressing mutants SUR1(R1379C) or SUR1(R1379L) was potentiated to a large extent (Figs. Login to comment
121 After treatment of SUR1-, SUR1(M1289T)-, SUR2A-, and SUR2B-expressing HEK293 cells (A and B) or of SUR1, SUR1(R1379C), and SUR1(R1379L) cells (C) with 17beta-estradiol (100 òe;mol/liter, 24 h), cell detachmentorchangesinnuclearmorphologyweredeterminedandcomparedwiththeresultsobtainedwith pcDNA control cells (please note the different scales in A and C). Login to comment
147 HEK293 cells stably expressing SUR1, SUR1(M1289T), SUR1(R1379C), or pcDNA control cells (A) were compared with cells from the clonal beta-cell lines HIT-T15 and RIN-m5F (B) or to isolated islets from SUR1-expressing wild type mice (SUR1wt) or SUR1KO mice (C) after treatment with 100 òe;mol/liter 17beta-estradiol (E2) or solvent (solv.) Login to comment
186 This SUR1-dependent effect of 17beta-estradiol is either abolished by mutation M1289T or enhanced by mutations R1379C or R1379L in SUR1. Login to comment
229 To see whether SUR1-mediated apoptosis is linked with ATP hydrolysis, we explored the effects of mutations R1379C and R1379L in nucleotide binding fold 2 of SUR1 on 17beta-estradiol action. Login to comment

PMID: 16885549 [PubMed] Babenko AP et al: "Activating mutations in the ABCC8 gene in neonatal diabetes mellitus."

No. Sentence Comment

43 A homology model26 of the human SUR1 core was used to map the mutant residues.27 Results ABCC8 Mutations in Patients with Permanent or Transient Neonatal Diabetes We identified seven heterozygous ABCC8 mutations in 9 of 34 patients with neonatal diabetes: L213R and I1424V in 2 with permanent neonatal diabetes and C435R, L582V, H1023Y, R1182Q, and R1379C in patients with transient neonatal diabetes. Login to comment
48 The L213R, H1023Y, and I1424V were noninherited mutations, as were the L582V and R1379C mutations in one family each. Login to comment
54 Diabetes developed in the father of the proband (with an R1379C mutation) in Family 17 when he was 32 years old, and he is receiving glyburide. Login to comment
55 The R1379C allele was also identified in the proband`s paternal grandmother who had had gestational diabetes and is currently being treated with diet and in a paternal great-aunt who was given a diagnosis of diabetes at 44 years of age and is currently being treated with sulfonylureas. Login to comment
67 After identification of the mutations in the patients with permanent neonatal diabetes, glyburide therapy was initiated and found to be successful and insulin was discontinued after 2 days in the proband from Family 12 and after 15 days in the proband from A Permanent Neonatal Diabetes B Transient Neonatal Diabetes NN NN NN NN NN NN NN NNNM NM NM NM NM NMNM NM NM* NM* NA NA NA NA NANANANANA NA NA NA NA Family 12 (L213R) NNNN NM Family 36 (L582V) 16 NN NN NNNM NMNM Family 28 (H1023Y) Family 34 (R1182Q) Family 16 (L582V) Family 17 (R1379C) Family 16 (I1424V) I II III I II III IV V 1 1 2 1 2 3 4 5 2 1 2 1 2 1 2 1 2 3 4 5 6 7 3 1 4 6 NNNN NN NNNM NMNM* Family 13 (C435R) Family 19 (R1379C) Transient Neonatal Diabetes Figure 1. Login to comment
42 A homology model26 of the human SUR1 core was used to map the mutant residues.27 Results ABCC8 Mutations in Patients with Permanent or Transient Neonatal Diabetes We identified seven heterozygous ABCC8 mutations in 9 of 34 patients with neonatal diabetes: L213R and I1424V in 2 with permanent neonatal diabetes and C435R, L582V, H1023Y, R1182Q, and R1379C in patients with transient neonatal diabetes. Login to comment
47 The L213R, H1023Y, and I1424V were noninherited mutations, as were the L582V and R1379C mutations in one family each. Login to comment
53 Diabetes developed in the father of the proband (with an R1379C mutation) in Family 17 when he was 32 years old, and he is receiving glyburide. Login to comment
66 After identification of the mutations in the patients with permanent neonatal diabetes, glyburide therapy was initiated and found to be successful and insulin was discontinued after 2 days in the proband from Family 12 and after 15 days in the proband from A Permanent Neonatal Diabetes B Transient Neonatal Diabetes NN NN NN NN NN NN NN NN NM NM NM NM NM NM NM NM NM* NM* NA NA NA NA NA NA NA NA NA NA NA NA NA Family 12 (L213R) NN NN NM Family 36 (L582V) 16 NN NN NN NM NM NM Family 28 (H1023Y) Family 34 (R1182Q) Family 16 (L582V) Family 17 (R1379C) Family 16 (I1424V) I II III I II III IV V 1 1 2 1 2 3 4 5 2 1 2 1 2 1 2 1 2 3 4 5 6 7 3 1 4 6 NN NN NN NN NM NM NM* Family 13 (C435R) Family 19 (R1379C) Transient Neonatal Diabetes Figure 1. Login to comment
92 Mutation Sex Wk of Gestation Birth Weight At Diagnosis At Metabolic Testing Current Treatment Age Weight Presentation Glucose Age Height Weight Insulin g (percentile) days g mmol/liter yr cm (SD)ߤ kg (percentile) U/kg/day Permanent neonatal diabetes 12 L213R Male 41 3065 (22) 125 5320 Polyuria, polydipsia 28.6 4.75 107.5 (0) 17 (50) 0.12 Glb, 10 mg/day 16 I1424V Male 40 3080 (25) 33 3360 Ketoacidosis 66 16.5 178 (+0.9) 69 (85) 0.88 Glb, 15 mg/day Transient neonatal diabetes 13 C435R Male 40 3040 (25) 32 3575 Polyuria, polydipsia 44.5 4.75 108.8 (+0.5) 17.5 (75) 16 L582V Male 40 3350 (50) 15 3210 Polyuria, polydipsia 51.4 5.25 117 (+1.9) 18.4 (50) 17 R1379C Female 40 2050 (<3) 3 2100 Hyperglycemia 6.9 5.25 114.5 (+1.6) 19.5 (82) 19 R1379C Female 40 2330 (<3) 60 4900 Polyuria, polydipsia 22 15.7 158 (-0.8) 54 (70) 1.2 Glb, 10 mg/day 28 H1023Y Male 40 3400 (55) 21 NA Ketoacidosis 37.8 16 180 (+1.2) 59.5 (60) 0.5 Glp, 10 mg/day 34 R1182Q Male 34 1830 (8) 4 1680 Hyperglycemia 13.6 2 82 (-1.5) 10.3 (8) 36 L582V Male 40 3570 (67) 74 6100 Polyuria, polydipsia 34 1.8 92 (+2) 14 (90) * Glb denotes glyburide, NA not available, and Glp glipizide. Login to comment

PMID: 18346985 [PubMed] Tarasov AI et al: "A rare mutation in ABCC8/SUR1 leading to altered ATP-sensitive K+ channel activity and beta-cell glucose sensing is associated with type 2 diabetes in adults."

No. Sentence Comment

83 (E), wild type; (F), Y356C; (f), K1521N; (Ⅺ), H1023Y; (Œ), R248Q; (‚), L582V; (ૺ), R1379C. Login to comment
120 To test whether the mutations associated with type 2 diabetes might affect stimulus-secretion coupling in beta-cells, we next measured the sensitivity to ATP of recombinant KATP channels carrying SUR-Y356C, -R248Q, and -K1521N and compared these to the ATP sensitivity of TND-associated mutants (4), L582V, H1023Y, and R1379C. Login to comment

PMID: 25306193 [PubMed] Alkorta-Aranburu G et al: "Phenotypic heterogeneity in monogenic diabetes: the clinical and diagnostic utility of a gene panel-based next-generation sequencing approach."

No. Sentence Comment

57 Patient Gender Gene Nucleotide Amino acid Zygosity 1 M ABCC8 c.3440TNG, c.4135CNT p.Leu1147Arg, p.Arg1379Cys Comp HET 2 M EIF2AK3 c.1267dup p.Ile423Asnfs*26 HOMO 3 M GATA6 c.1088_1098del p.Gln363Argfs*96 HET 4 F KCNJ11 c.602GNA p.Arg201His HET 5 F KCNJ11 c.5TNC p.Leu2Pro HET 6 M RFX6 c.779ANC p.Lys260Thr HOMO 7 F FOXP3 c.1044+5GNA p.? Login to comment