DIMINISHED FRACTION OF BLOCKABLE ATP-SENSITIVE K+ CHANNELS IN ISLETS TRANSPLANTED INTO DIABETIC MICE

Citation
B. Soria et al., DIMINISHED FRACTION OF BLOCKABLE ATP-SENSITIVE K+ CHANNELS IN ISLETS TRANSPLANTED INTO DIABETIC MICE, Diabetes, 45(12), 1996, pp. 1755-1760
Citations number
34
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Journal title
ISSN journal
00121797
Volume
45
Issue
12
Year of publication
1996
Pages
1755 - 1760
Database
ISI
SICI code
0012-1797(1996)45:12<1755:DFOBAK>2.0.ZU;2-E
Abstract
The reasons for the poor outcome of islet transplantation in diabetic patients are not well known; a better understanding of the pathophysio logy of transplanted islets is needed. To study the mechanism coupling secretagogue stimuli with insulin release in transplanted islets, we determined the effects of glucose, tolbutamide, and carbamylcholine on the beta-cell membrane potential and cytosolic calcium concentrations ([Ca2+](i)) of islets syngeneically transplanted into normal and stre ptozocin-induced diabetic mice. In both groups, normoglycemia was main tained after transplantation. Islets transplanted into normal recipien ts showed similar changes in beta-cell membrane potential and [Ca2+](i ) oscillations to those in control islets. In contrast, when islets we re transplanted into diabetic mice, bursts of electrical activity were triggered at lower glucose concentrations (5.6 mmol/l) than in contro l islets (11 mmol/l), and maximal electrical activity was achieved at lower glucose concentrations (11 mmol/l) than in control islets (22 mm ol/l). When membrane potential was plotted as a function of glucose co ncentration, the dose-response curve was shifted to the left. Compared with control islets, glucose-induced [Ca2+](i) oscillations were broa der in duration (22.3 +/- 0.6 s vs. 118.1 +/- 12.6 s; P < 0.01) and hi gher in amplitude (135 +/- 36 nmol/l vs. 352 +/- 36 nmol/l; P < 0.01). Glucose supersensitivity was attributed to a resting decrease in the fraction of blockable ATP-sensitive K+ (K-ATP(+)) channels in transpla nted islets that maintained normoglycemia with a limited beta-cell mas s.