GLUCOSE-STIMULATED ELEVATION OF CYTOPLASMIC CALCIUM IS DEFECTIVE IN THE DIABETIC CHINESE-HAMSTER ISLET B-CELL

To characterize insulin release and cytoplasmic free Ca2+ ([Ca2+](i)) levels in the diabetic Chinese hamster islet B cell, islets from genet ically normal (subline M) and diabetic (subline L) hamsters were colla genase isolated. Insulin release and glucose utilization (conversion o f D-[5-H-3]glucose to (H2O)-H-3) were measured in whole islets; [Ca2+] (i) levels were measured in single islet cells using fura-2. The Ca2channel agonist, 12 mmol/l perchlorate, ClO4-, increased the subnormal insulin response during 20 mmol/l glucose perifusion, but did not nor malize it. Glucose utilization measured over a 2-h period was normal. Glucose induced an initial decrease and then a rise in [Ca2+](i) in 85 % of the normal (presumably B) cells. In diabetic cells, the [Ca2+](i) response was delayed, subnormal and only observed in 23% of the cells . When perchlorate or another Ca2+ channel agonist, 10 mu mol/l CGP 28 392, was added with glucose, a larger proportion of the diabetic cells (61-67%) showed increased [Ca2+]i and the mean [Ca2+]i response was n ot different from normal. However, neither perchlorate nor CGP 28392 c ould normalize glucose-stimulated insulin release, and K+-induced insu lin release was decreased in diabetic islets. The K+-induced [Ca2+](i) rise was essentially normal in all the diabetic islet cells. Therefor e, the diabetic hamster islet appears to metabolize glucose normally, but has a diminished insulin response to glucose and K+. The Ca2+ chan nel agonists markedly improve the subnormal [Ca2+](i) response but not the insulin response. Glucose-induced elevation of [Ca2+](i) and exoc ytosis appear defective in the diabetic Chinese hamster B cell.