An insulinotropic effect of vitamin D analog with increasing intracellular Ca2+ concentration in pancreatic beta-cells through nongenomic signal transduction.
The effect of 1alpha,25-dihydroxylumisterol3 (1alpha,25(OH)2lumisterol3) on insulin release from rat pancreatic beta-cells was measured to investigate the nongenomic action of vitamin D via the putative membrane vitamin D receptor (mVDR). 1Alpha,25(OH)2lumisterol3, a specific agonist of mVDR, dose-dependently augmented 16.7 mM glucose-induced insulin release from rat pancreatic islets and increased the intracellular Ca2+ concentration ([Ca2+]i), though not increasing Ca2+ efficacy in the exocytotic system. These effects were completely abolished by an antagonist of mVDR, 1beta,25-dihydroxyvitamin D3 (1beta,25(OH)2D3), or by a blocker of voltage-dependent Ca2+ channels, nitrendipine. Moreover, both [Ca2+]i elevation, caused by membrane depolarization, and sufficient intracellular glucose metabolism are required for the expression of these effects. 1Alpha,25(OH)2lumisterol3, therefore, has a rapid insulinotropic effect, through nongenomic signal transduction via mVDR, that would be dependent on the augmentation of Ca2+ influx through voltage-dependent Ca2+ channels on the plasma membrane, being also linked to metabolic signals derived from glucose in pancreatic beta-cells. However, further investigations will be needed to discuss physiologically the meaning of insulinotropic effects of vitamin D through mVDR.
Kajikawa
M
M
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan. kajikawa@metab.kuhp.kyoto-u.ac.jp
Ishida
H
H
Fujimoto
S
S
Mukai
E
E
Nishimura
M
M
Fujita
J
J
Tsuura
Y
Y
Okamoto
Y
Y
Norman
A W
AW
Seino
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003981:Diazoxide / Q000494:pharmacology; D004558:Electric Stimulation; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007425:Intracellular Membranes / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D010539:Permeability; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D014807:Vitamin D / Q000031:analogs & derivatives*
C121609:1,25-dihydroxylumisterol(3); D007328:Insulin; D014807:Vitamin D; D005947:Glucose; D003981:Diazoxide; D011188:Potassium; D002118:Calcium; D004875:Ergosterol