Effects of insulin-like growth factors (IGF) on pancreatic islet function in IGF binding protein-1 transgenic mice.
We have previously reported fasting hyperglycaemia, hyperinsulinaemia, and glucose intolerance in transgenic (Tg) mice which overexpress rat insulin-like growth factor binding protein-1 (IGFBP-1). An increase in pancreatic islet size and number was also observed in this model. Islets from Tg mice had relatively more beta cells and less alpha cells than islets from wild-type (Wt) mice. These observations prompted us to investigate the effects of glucose and insulin-like growth factor-I (IGF-I) on insulin and glucagon release by isolated islets from Tg and Wt mice. Under basal glucose conditions, islets from Tg mice released significantly more insulin and less glucagon than islets from Wt mice. This difference was significant even when corrected for the increased size and cellularity of islets from Tg mice. A dose-dependent increase in insulin release was observed with increased glucose concentrations in both Wt and Tg mice. At all but the highest glucose concentration, islets from Tg mice released significantly greater amounts of insulin than islets from Wt mice. Addition of IGF-I to islet incubations resulted in a dose-dependent increase in insulin release. However, the effect of IGF-I on islets from Tg mice was reduced compared to islets from Wt mice. From these data we conclude that IGF-I stimulates rather than inhibits insulin secretion in isolated murine islets. Furthermore, an intrinsic defect in pancreatic islet insulin release is not responsible for the glucose intolerance in Tg mice. Rather, the data suggest that the hyperglycaemia or local effects of IGFBP-1 over-expression results in a state of enhanced insulin secretion which persists under short-term in vitro culture conditions.
Dheen
S T
ST
Department of Internal Medicine, University of Manitoba, winnipeg, Canada.
Rajkumar
K
K
Murphy
L J
LJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D013002:Somatomedins / Q000494:pharmacology*
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D013002:Somatomedins; D005934:Glucagon; D005947:Glucose