title: Glucose-stimulated elevation of cytoplasmic calcium is defective in the diabetic Chinese hamster islet B cell.
abstract: To characterize insulin release and cytoplasmic free Ca2+ ([Ca2+]i) levels in the diabetic Chinese hamster islet B cell, islets from genetically normal (subline M) and diabetic (subline L) hamsters were collagenase isolated. Insulin release and glucose utilization (conversion of D-[5-(3H)]glucose to 3H2O) were measured in whole islets; [Ca2+]i levels were measured in single islet cells using fura-2. The Ca2+ channel agonist, 12 mmol/l perchlorate, ClO4-, increased the subnormal insulin response during 20 mmol/l glucose perifusion, but did not normalize 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 mumol/l CGP 28392, was added with glucose, a larger proportion of the diabetic cells (61-67%) showed increased [Ca2+]i and the mean [Ca2+]i response was not different from normal. However, neither perchlorate nor CGP 28392 could normalize glucose-stimulated insulin release, and K(+)-induced insulin release was decreased in diabetic islets. The K(+)-induced [Ca2+]i rise was essentially normal in all the diabetic islet cells. Therefore, the diabetic hamster islet appears to metabolize glucose normally, but has a diminished insulin response to glucose and K+. The Ca2+ channel agonists markedly improve the subnormal [Ca2+]i response but not the insulin response. Glucose-induced elevation of [Ca2+]i and exocytosis appear defective in the diabetic Chinese hamster B cell.
authors.affiliation: Department of Histology and Cell Biology, Umeå University, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Lindström
authors.forename: J
authors.initials: J
authors.lastname: Sehlin
authors.forename: B J
authors.initials: BJ
authors.lastname: Frankel
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D003593:Cytoplasm / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism*; D005456:Fluorescent Dyes; D016257:Fura-2; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010472:Perchlorates / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017670:Sodium Compounds / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D005456:Fluorescent Dyes; D007328:Insulin; D010472:Perchlorates; D011725:Pyridines; D017670:Sodium Compounds; C040525:CGP 28392; C031068:sodium perchlorate; D005947:Glucose; D011188:Potassium; D002118:Calcium; D016257:Fura-2