Autocrine anti-apoptotic and proliferative effects of insulin in pancreatic beta-cells.
Insulin and glucose inhibited apoptosis in the MIN6 insulin-secreting cell line. The protective effect of 25 mM glucose was prevented by an anti-insulin antibody and this antibody-induced increase in apoptosis was reversed by the presence of excess insulin. Glucose stimulated MIN6 cell proliferation and this was inhibited by blockade of insulin secretion, by an anti-insulin antibody and by phosphatidylinositol-3 kinase (PI-3K) inhibition. Furthermore, MIN6 cell proliferation was stimulated by depolarising concentrations of KCl and by insulin itself. These data indicate that insulin secreted by beta-cells in response to elevated glucose exerts autocrine effects to protect against apoptosis and stimulate proliferation, and suggest that the insulin signalling cascade, through the PI-3K pathway, may be an effective means of maintaining beta-cell mass in diabetes.
Muller
Dany
D
Beta Cell Development and Function Group, School of Biomedical and Health Sciences, King's College London, Guy's Campus, London SE1 1UL, UK. dany.muller@kcl.ac.uk
Jones
Peter M
PM
Persaud
Shanta J
SJ
D017209:Apoptosis / Q000187:drug effects; D019898:Autocrine Communication; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*
D007328:Insulin; D005947:Glucose