Insulin secretagogues, but not glucose, stimulate an increase in [Ca2+]i in the fetal rat beta-cell.
Fetal pancreatic islets release insulin poorly in response to glucose; however, the cellular mechanism for this is controversial. By using fura 2 to measure changes in the cytoplasmic free Ca2+ concentration ([Ca2+]i) in beta-cells, we have examined islets from fetal, neonatal, and adult rats to determine the ability of glucose and other secretagogues to cause an increase in [Ca2+]i. The effects of glucose (20 mmol/l), glyceraldehyde (20 mmol/l), leucine (20 mmol/l), arginine (20 mmol/l), and the channel effectors glipizide (50 mumol/l), BAY K8644 (2 mumol/l), diazoxide (300 mumol/l), and verapamil (20 mumol/l) on changes in [Ca2+]i were studied. In both the fetal and the mature islet, glyceraldehyde, leucine, arginine, glipizide, and BAY K8644 caused an increase in [Ca2+]i. In mature islets, glucose also increased [Ca2+]i; however, in the fetal islet, glucose had no effect on [Ca2+]i. The stimulus-induced increases in [Ca2+]i in fetal and adult islets were both significantly inhibited by the addition of either diazoxide or verapamil. Similar results were obtained when insulin secretion was measured. Our data show that various secretagogues are able to stimulate fetal islets and cause an increase in [Ca2+]i. Glucose, however, fails to cause an increase in [Ca2+]i in the fetal islet. Hence, the immature insulin secretory response to glucose by the fetal islet is due to the inability of the fetal beta-cell to translate glucose stimulation into the increase in [Ca2+]i required for exocytosis of the insulin granule.
Weinhaus
A J
AJ
Department of Medicine, University of Sydney, Australia.
Poronnik
P
P
Cook
D I
DI
Tuch
B E
BE
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002478:Cells, Cultured; D003981:Diazoxide / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D005913:Glipizide / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D005985:Glyceraldehyde / Q000494:pharmacology*; D007150:Immunohistochemistry; D007328:Insulin / Q000032:analysis / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D007930:Leucine / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
D007328:Insulin; D005985:Glyceraldehyde; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D001120:Arginine; D014700:Verapamil; D007930:Leucine; D005947:Glucose; D003981:Diazoxide; D002118:Calcium; D005913:Glipizide