INSULIN SECRETAGOGUES, BUT NOT GLUCOSE, STIMULATE AN INCREASE IN [CA2-CELL(](I) IN THE FETAL RAT BETA)

Fetal pancreatic islets release insulin poorly in response to glucose; however, the cellular mechanism for this is controversial. By using f ura 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 secretag ogues to cause an increase in [Ca2+](i). The effects of glucose (20 mm ol/l), glyceraldehyde (20 mmol/l), leucine (20 mmol/l), arginine (20 m mol/l), and the channel effecters glipizide (50 mu mol/l), BAY K8644 ( 2 mu mol/l), diazoxide (300 mu mol/l), and verapamil (20 mu mol/l) on changes in [Ca2+](i) were studied. In both the fetal and the mature is let, glyceraldehyde, leucine, arginine, glipizide, and BAY K8644 cause d 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 is lets were both significantly inhibited by the addition of either diazo xide or verapamil. Similar results were obtained when insulin secretio n was measured. Our data show that various secretagogues are able to s timulate fetal islets and cause an increase in [Ca2+](i). Glucose, how ever, fails to cause an increase in [Ca2+](i) in the fetal islet, Henc e, the immature insulin secretory response to glucose by the fetal isl et 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.