PMID- 10499529 OWN - NLM STAT- MEDLINE DCOM- 19991012 LR - 20181217 IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 140 IP - 10 DP - 1999 Oct TI - An insulinotropic effect of vitamin D analog with increasing intracellular Ca2+ concentration in pancreatic beta-cells through nongenomic signal transduction. PG - 4706-12 AB - 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. FAU - Kajikawa, M AU - Kajikawa M AD - Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan. kajikawa@metab.kuhp.kyoto-u.ac.jp FAU - Ishida, H AU - Ishida H FAU - Fujimoto, S AU - Fujimoto S FAU - Mukai, E AU - Mukai E FAU - Nishimura, M AU - Nishimura M FAU - Fujita, J AU - Fujita J FAU - Tsuura, Y AU - Tsuura Y FAU - Okamoto, Y AU - Okamoto Y FAU - Norman, A W AU - Norman AW FAU - Seino, Y AU - Seino Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (1,25-dihydroxylumisterol(3)) RN - 0 (Insulin) RN - 1406-16-2 (Vitamin D) RN - IY9XDZ35W2 (Glucose) RN - O5CB12L4FN (Diazoxide) RN - RWP5GA015D (Potassium) RN - SY7Q814VUP (Calcium) RN - Z30RAY509F (Ergosterol) SB - IM MH - Animals MH - Calcium/*metabolism MH - Diazoxide/pharmacology MH - Electric Stimulation MH - Ergosterol/*analogs & derivatives/pharmacology MH - Glucose/pharmacology MH - Insulin/*metabolism MH - Insulin Secretion MH - Intracellular Membranes/*metabolism MH - Islets of Langerhans/drug effects/*metabolism MH - Male MH - Osmolar Concentration MH - Permeability MH - Potassium/pharmacology MH - Rats MH - Rats, Wistar MH - Signal Transduction/*physiology MH - Vitamin D/*analogs & derivatives EDAT- 1999/09/28 00:00 MHDA- 1999/09/28 00:01 CRDT- 1999/09/28 00:00 PHST- 1999/09/28 00:00 [pubmed] PHST- 1999/09/28 00:01 [medline] PHST- 1999/09/28 00:00 [entrez] AID - 10.1210/endo.140.10.7025 [doi] PST - ppublish SO - Endocrinology. 1999 Oct;140(10):4706-12. doi: 10.1210/endo.140.10.7025.