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Imidazolines and the Pancreatic B‐Cell: Actions and Binding Sites
Author(s) -
RUSTENBECK I.,
KÖPP M.,
RATZKA P.,
LEUPOLT L.,
HASSELBLATT A.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb09365.x
Subject(s) - chemistry , binding site , microbiology and biotechnology , biochemistry , biology
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 Ca 2+ channels (−40 to −30 mV). An increase in cytoplasmic Ca 2+ concentration was induced by phentolamine and much less so by idazoxan. Activation of protein kinase C, a possible mechanism to amplify Ca 2+ ‐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 K ATP channels, which may be the correlate of non‐adrenergic imidazoline binding sites which were characterized in insulin‐secreting HIT cells. Whether incomplete closure of K ATP channels by idazoxan or additional effects are responsible for the requirement of high glucose to stimulate secretion remains to be clarified.