Calcium as a second messenger of the action of transforming growth factor-beta on insulin secretion.
In MIN6 insulinoma cells, transforming growth factor-beta (TGF-beta) 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-beta 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-beta did not raise [Ca2+]c, whereas both carbachol and depolarizing concentration of potassium 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 increase in insulin secretion and the effect of TGF-beta was blocked by either nifedipine or nickel chloride. TGF-beta did not stimulate insulin secretion in the presence of 100 microM diazoxide, whereas both carbachol and 40 mM potassium chloride significantly increased insulin secretion. These results suggest that TGF-beta 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-beta on insulin secretion.
Ishiyama
N
N
Department of Laboratory Medicine, Gunma University School of Medicine, Maebashi, Japan.
Shibata
H
H
Kanzaki
M
M
Shiozaki
S
S
Miyazaki
J
J
Kobayashi
I
I
Kojima
I
I
D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007295:Inositol Phosphates; D007328:Insulin; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C022838:nickel chloride; D009532:Nickel; D000242:Cyclic AMP; D009543:Nifedipine; D002118:Calcium