Calcium as a second messenger of the action of transforming growth factor-β on insulin secretion

In MIN6 insulinoma cells, transforming growth factor-β (TGF-β) induced the oscillatory elevation of the cytoplasmic free calcium concentration, [Ca²⁺](c), in the presence of 5.5 mM glucose. The increase in [Ca²⁺](c) induced by TGF-β was totally dependent on calcium entry and attenuated by nifedipine or nickel chloride. In contrast, carbachol elevated [Ca²⁺](c) in the presence of nickel chloride. When the plasma membrane was hyperpolarized by diazoxide, TGF-β did not raise [Ca²⁺](c), whereas both carbachol and depolarizing concentration of potassium elevated [Ca²⁺](c) under the same conditions. TGF-β did not affect either the cellular cyclic AMP or inositol trisphosphate levels. In the presence of 5.5 mM glucose, TGF-β induced a 3-fold increase in insulin secretion and the effect of TGF-β was blocked by either nifedipine or nickel chloride. TGF-β did not stimulate insulin secretion in the presence of 100 μM diazoxide, whereas both carbachol and 40 mM potassium chloride significantly increased insulin secretion. These results suggest that TGF-β induces the oscillatory elevation of [Ca²⁺](c) in MIN6 cells by stimulating calcium entry via voltage-dependent calcium channels. Calcium is an intracellular messenger of the action of TGF-β on insulin secretion.