Regulatory effect of 1,25-dihydroxyvitamin D3 on insulin release and calcium handling via the phospholipid pathway in islets from vitamin D-deficient rats.

The effect of 10−8 M 1,25-dihydroxyvitamin D3 [1,25 (OH)2D3] on the phosphoinositide pathway, was studied on [3H] inositol and 45Ca2+ efflux and on insulin release of islets from vitamin D-deficient rats, during an acetylcholine (Ach) stimulus in perifusion. The insulin release, which was low in vitamin D-deficient rats, was enhanced by this treatment. The 3H flux, reflecting phosphoinositide breakdown, was also increased. The 45Ca2+ flux was stimulated both during the first 14 min peak (mobilization of IP3-sensitive reticular Ca2+ stores) and during the following sustained small elevation of 45Ca2+ flux, reflecting protein kinase C (PKC) activation and consequently increased phosphorylation of Ca2+ channel proteins. These effects were larger during perifusions performed in the presence of glucose which is known to open Ca2+ channels, suggesting a synergistic influence of glucose and 1,25(OH)2D3. This positive influence of 1,25(OH)2D3 on Ca2+ entry by Ca2+ channels was confirmed by the use of nifedipine — a Ca2+ channel blocker-which suppressed the 45Ca2+ flux and lowered insulin secretion. Moreover, the sustained 45Ca2+ flux also disappeared in islets from vitamin D-deficient rats supplemented by 1,25(OH)2D3 but perifused without extracellular Ca2+, supporting the hypothesis of 1,25(OH)2D3-induced activation of PKC. Thus, 1,25(OH)2D3 may provide supplementary calcium to the B cell by regulating the intracellular signalling processes involving phospholipid metabolism, PKC induction, Ca2+ mobilization and Ca2+ entry by Ca2+ channels.