Effects of thapsigargin, an intracellular CA2+ pump inhibitor, on insulin release by rat pancreatic B-cell.
This is the first report as to the effects of thapsigargin (Tg), an inhibitor of intracellular Ca2+ pumps, on insulin release by pancreatic B-cells. Tg does not alter basal insulin release by the isolated islets, with 3 mM glucose. However, it potentiates high glucose-induced insulin release: potentiation of the first phase response is dose-related in a concentration range of 1.3-40 microM. In isolated B-cells, Tg causes a minimal rise in basal cytosolic free calcium concentration ([Ca2+]i) and eliminates high glucose-induced initial lowering of [Ca2+]i. Tg does not alter glucose oxidation by the islets and the islet insulin content. An elimination of glucose-induced sequestration of Ca2+ into Tg-sensitive intracellular pool(s) is considered to be the cause of Tg potentiation of glucose effect on insulin release.
Aizawa
T
T
Department of Geriatrics, Endocrinology and Metabolism, Shinshu University School of Medicine, Matsumoto, Japan.
Yada
T
T
Asanuma
N
N
Sato
Y
Y
Ishihara
F
F
Hamakawa
N
N
Yaekura
K
K
Hashizume
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin
D007328:Insulin; D013729:Terpenes; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D005947:Glucose; D002118:Calcium