ABCMdb

PMID: 20863361

Porksen S, Laborie LB, Nielsen L, Louise Max Andersen M, Sandal T, de Wet H, Schwarcz E, Aman J, Swift P, Kocova M, Schonle EJ, de Beaufort C, Hougaard P, Ashcroft F, Molven A, Knip M, Mortensen HB, Hansen L, Njolstad PR
Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies.
BMC Endocr Disord. 2010 Sep 23;10:16., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCC8 p.Arg1530Cys Functional analyses of recombinant K-ATP channels showed that R1530C markedly reduced the sensitivity of the KATP channel to inhibition by MgATP. Login to comment 89 ABCC8 p.Arg1530Cys We studied the functional effects of the SUR1-R1530C mutation by expressing recombinant KATP channels in Xenopus oocytes. Login to comment 91 ABCC8 p.Arg1530Cys In contrast, in oocytes expressing SUR1-R1530C mutant channels significant resting whole-cell KATP currents were present in the absence of metabolic inhibition (Fig. 2). Login to comment 100 ABCC8 p.Arg1530Cys Although functional analyses showed that the mutant channel was highly sensitive to sulfonylureas, there was no clinical effect on metabolic control or insulin requirement after four weeks of glibenclamide treatment (1.0-1.2 mg/kg/24h) 8 years after Table 2 Clinical characteristics of the two study participants who tested negative for autoantibodies (GADA, IA-2A, and ICA) at 1 month and who converted to positivity for GADA (patient 2) at 12 months or IA-2A (patient 24 (carrier of the Arg1530Cys mutation of the ABCC8)) at 6 and 12 months after the diagnosis of type 1 diabetes Patient Age (years) Sex BMI (kg/m 2 ) HbA1C0 (%) IDAA1C 1 IDAA1C 6 IDAA1C 12 Ins dose1 (U/kg/day) ins dose6 (U/kg/day) Ins dose12 (U/kg/day) Cpep1 (pmol/L) Cpep6 (pmol/L) Cpep12 (pmol/L) BGstim1 (mmol/L) BGstim6 (mmol/L) BGstim12 (mmol/L) 2 16.3 female 17 10.9 Na 11.1 11.7 0.54 0.73 0.59 120 10 10 14.2 20.7 13.2 24 14 male 16.4 12.4 11.3 10.6 12.8 0.63 0.73 0.98 356 308 218 13.9 21 20.6 Abbreviations: Na, not available; BMI, body mass index; HBA1C0; HBA1C at diagnosis; IDAA1C 1, Insulin Dose Adjusted HbA1c (IDAA1C) at 1 month; IDAA1C 6, IDAA1C at 6 months; IDAA1C 12, IDAA1C at 12 months;; Ins dose1, insulin dose at 1 month; Ins dose6, insulin dose at 6 months; Ins dose12, insulin dose at 12 months; Cpep1, stimulated C-peptide at 1 month, Cpep6, stimulated C-peptide at 6 months; Cpep12, stimulated C-peptide at 12 months; BGstim1, 90 min glucose at 1 month; BGstim6, 90 min glucose at 6 months; BGstim12, 90 min glucose at 12 months; (HbA1c (%) + [4 x insulin dose (U/Kg/24h)) (pmol/L) A C E B D (pmol/L) Figure 1 Comparison of disease course in autoantibody-negative and autoantibody-positive children: A: 12 months after disease onset, the residual beta cell function in autoantibody-negative patients was twofold higher than in autoantibody-positive patients (p = 0.002). Login to comment 107 ABCC8 p.Arg1530Cys Meal-stimulated GLP-1 and GIP did not differ between the subject carrying the R1530C mutation and non-carriers (data not shown). Login to comment 123 ABCC8 p.Arg1530Cys ABCC8 p.Arg1530Cys At study entry the diagnosis of wt R1531C azide Tolbutamide 0.5 µA 0.5 µA Figure 2 Tolbutamide response in SUR1-R1530C. Login to comment 124 ABCC8 p.Arg1530Cys Whole-cell currents recorded from Xenopus oocytes coexpressing Kir6.2 and either SUR1 (WT) or SUR1-R1530C in response to voltage steps of +20 mV from a holding potential of -10 mV. Login to comment 126 ABCC8 p.Arg1530Cys Figure 3 Tolbutamide response in SUR1-R1530C. Login to comment 137 ABCC8 p.Arg1530Cys We did not find pathogenic mutations in INS or KCNJ11, but one subject had a heterozygous mutation (R1530C) in SUR1 encoded by ABCC8. Login to comment