Effects of glucose, exogenous insulin, and carbachol on C-peptide and insulin secretion from isolated perifused rat islets.
Isolated perifused rat islets were stimulated with glucose, exogenous insulin, or carbachol. C-peptide and, where possible, insulin secretory rates were measured. Glucose (8-10 mm) induced dose-dependent and kinetically similar patterns of C-peptide and insulin secretion. The addition of 100 nm bovine insulin had no effect on C-peptide release in response to 8-10 mm glucose stimulation. The addition of 100 nm bovine insulin or 500 nm human insulin together with 3 mm glucose had no stimulatory effect on C-peptide secretion rates from perifused rat islets. Stimulation with carbachol plus 7 mm glucose enhanced both C-peptide and insulin secretion, and the further addition of 100 nm bovine insulin had no inhibitory effect on C-peptide secretory rates under this condition. Perifusion studies using pharmacologic inhibitors (genistein and wortmannin) of the kinases thought to be involved in insulin signaling potentiated 10 mm glucose-induced secretion. The results support the following conclusions. 1) C-peptide release rates accurately reflect insulin secretion rates from collagenase-isolated, perifused rat islets. 2) Exogenously added bovine insulin exerts no inhibitory effect on release to several agonists including glucose. 3) In the presence of 3 mm glucose, exogenously added bovine or human insulin do not stimulate endogenous insulin secretion.
Zawalich
Walter S
WS
Yale University School of Nursing, New Haven, Connecticut 06536-0740, USA. Walter.Zawalich@Yale.Edu
Zawalich
Kathleen C
KC
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002096:C-Peptide / Q000378:metabolism*; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019833:Genistein / Q000494:pharmacology; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077191:Wortmannin
D000730:Androstadienes; D002096:C-Peptide; D007328:Insulin; D002217:Carbachol; D019833:Genistein; D005947:Glucose; D000077191:Wortmannin