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 in 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.
Billaudel
B J
BJ
Laboratoire d'Endocrinologie, Université de Bordeaux I, France.
Bourlon
P M
PM
Sutter
B C
BC
Faure-Dussert
A G
AG
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002132:Calcium Radioisotopes; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014808:Vitamin D Deficiency / Q000378:metabolism*
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D007328:Insulin; D010743:Phospholipids; D011493:Protein Kinase C; D002117:Calcitriol; D009543:Nifedipine; D005947:Glucose; D000109:Acetylcholine; D002118:Calcium