Imidazolines and the Pancreatic B-Cell: Actions and Binding Sites
Article first published online: 6 FEB 2006
Annals of the New York Academy of Sciences
How to Cite
RUSTENBECK, I., KÖPP, M., RATZKA, P., LEUPOLT, L. and HASSELBLATT, A. (1999), Imidazolines and the Pancreatic B-Cell: Actions and Binding Sites. Annals of the New York Academy of Sciences, 881: 229–240. doi: 10.1111/j.1749-6632.1999.tb09365.x
- Issue published online: 6 FEB 2006
- Article first published online: 6 FEB 2006
ABSTRACT: Stimulation of insulin secretion by imidazoline compounds displays variable characteristics. Phentolamine (10–100 μM) increased secretion of perifused mouse islets at nonstimulatory glucose concentrations (5 mM) and even in the absence of glucose. Idazoxan (20–100 μM) elicited a moderate increase in insulin secretion, which required the presence of a stimulatory glucose concentration (10 mM). Phentolamine is therefore a stimulator of secretion in its own right, whereas idazoxan may be termed an enhancer of secretion. Both compounds inhibited the activity of ATP-dependent K+ channels in inside-out patches from B-cells; however, idazoxan achieved only an incomplete block. Both compounds depolarized the B-cell plasma membrane to an extent that permitted the opening of voltage-dependent Ca2+ channels (−40 to −30 mV). An increase in cytoplasmic Ca2+ concentration was induced by phentolamine and much less so by idazoxan. Activation of protein kinase C, a possible mechanism to amplify Ca2+-induced secretion, could not be verified for phentolamine. It thus appears that stimulation of insulin secretion by phentolamine is due to its blocking effect on KATP channels, which may be the correlate of non-adrenergic imidazoline binding sites which were characterized in insulin-secreting HIT cells. Whether incomplete closure of KATP channels by idazoxan or additional effects are responsible for the requirement of high glucose to stimulate secretion remains to be clarified.