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
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.