Insulin constitutively secreted by beta-cells is necessary for glucose-stimulated insulin secretion.
Four hypotheses have been posited on the role of insulin in glucose-stimulated insulin secretion; available evidence has supported insulin as being 1) essential, 2) a positive modulator, 3) a negative modulator, or 4) not necessary. Because circulating insulin levels in mice, before or after intraperitoneal glucose injection, are sufficient to elicit insulin responses in insulin-sensitive tissues, it is likely that beta-cell insulin receptors are continuously exposed to stimulating concentrations of insulin. To determine whether constitutively secreted insulin is necessary for glucose-stimulated insulin secretion, CD1 male mouse islets were incubated for 30 min at 4 degrees C in the absence (control) or presence of anti-insulin (1 micro g/ml) or anti-IgG (1 micro g/ml). Then islets were exposed to 3, 11, or 25 mmol/l glucose or to 20 mmol/l arginine. Nontreated islets exhibited first- and second-phase glucose-stimulated insulin secretion. Control and anti-IgG-treated islets, after a 5-min lag phase, increased their insulin secretion in 25 mmol/l glucose. Anti-insulin-treated islets secreted insulin at a basal rate in 3 or 25 mmol/l glucose buffers. Insulin secretion stimulated by 20 mmol/l arginine was the same in islets pretreated with either antibody and showed no lag phase. Taken together, these data suggest that constitutively secreted insulin is required and sufficient for beta-cells to maintain sensitivity to glucose.
Srivastava
Siddhartha
S
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Goren
H Joseph
HJ
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains
D007328:Insulin; D001120:Arginine; D005947:Glucose