TY - JOUR
T1 - Insulin secretagogues, but not glucose, stimulate an increase in [Ca2+](i) in the fetal rat β-cell
AU - Weinhaus, Anthony J.
AU - Poronnik, Philip
AU - Cook, David I.
AU - Tuch, Bernard E.
PY - 1995
Y1 - 1995
N2 - 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 β-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 μmol/l), BAY K8644 (2 μmol/l), diazoxide (300 μmol/l), and verapamil (20 μmol/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 β-cell to translate glucose stimulation into the increase in [Ca2+](i) required for exocytosis of the insulin granule.
AB - 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 β-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 μmol/l), BAY K8644 (2 μmol/l), diazoxide (300 μmol/l), and verapamil (20 μmol/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 β-cell to translate glucose stimulation into the increase in [Ca2+](i) required for exocytosis of the insulin granule.
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U2 - 10.2337/diab.44.1.118
DO - 10.2337/diab.44.1.118
M3 - Article
C2 - 7529202
AN - SCOPUS:0028861785
SN - 0012-1797
VL - 44
SP - 118
EP - 124
JO - Diabetes
JF - Diabetes
IS - 1
ER -