CALCIUM AS A 2ND-MESSENGER OF THE ACTION OF TRANSFORMING GROWTH-FACTOR-BETA ON INSULIN-SECRETION

In MIN6 insulinoma cells, transforming growth factor-beta (TGF-beta) i nduced the oscillatory elevation of the cytoplasmic free calcium conce ntration, [Ca2+](c), in the presence of 5.5 mM glucose. The increase i n [Ca2+](c) induced by TGF-beta was totally dependent on calcium entry and attenuated by nifedipine or nickel chloride. In contrast, carbach ol elevated [Ca2+](c) in the presence of nickel chloride. When the pla sma membrane was hyperpolarized by diazoxide, TGF-beta did not raise [ Ca2+](c), whereas both carbachol and depolarizing concentration of pot assium elevated [Ca2+](c) under the same conditions. TGF-beta did not affect either the cellular cyclic AMP or inositol trisphosphate levels . In the presence of 5.5 mM glucose, TGF-beta induced a 3-fold increas e in insulin secretion and the effect of TGF-beta was blocked by eithe r nifedipine or nickel chloride. TGF-beta did not stimulate insulin se cretion in the presence of 100 mu M diazoxide, whereas both carbachol and 40 mM potassium chloride significantly increased insulin secretion . These results suggest that TGF-beta induces the oscillatory elevatio n of [Ca2+](c) in MIN6 cells by stimulating calcium entry via voltage- dependent calcium channels. Calcium is an intracellular messenger of t he action of TGF-beta on insulin secretion.