Dissociation of phosphatidylinositol hydrolysis and insulin secretion of cultured mouse pancreatic islets.

The correlation between hydrolysis of phosphatidylinositol (PI) and insulin secretion was investigated in cultured mouse pancreatic islets. After prelabeling with [3H] glycerol or [3H] inositol, islets were incubated in the presence of different insulin secretagogues. Carbamylcholine induced a rapid decrease of PI-bound radioactivity concurrent with stimulation of insulin secretion, and both these responses were blocked by atropine. After culture at a low (3.3 mM), glucose concentration, carbamylcholine evoked PI hydrolysis, but no insulin secretory response was observed. Carbamylcholine induced PI hydrolysis also under Ca2+-free conditions, which blocked insulin secretion. Stimulation of insulin secretion with high glucose (16.7 mM), K+(25 mM), or arginine (10 mM), or addition of theophylline (5 mM) to high (16.7 mM) glucose, were associated with unchanged rates of PI hydrolysis. In labelling experiments, both carbamylcholine and glucose (16.7 mM) were found to stimulate the incorporation of [3H] inositol into islet PI. These results demonstrate that stimulation of muscarinic cholinergic receptors increases islet PI turnover. There was, however, no general correlation between islet PI turnover and insulin secretion.