title: Demonstration that the vitamin D metabolite 1,25(OH)2-vitamin D3 and not 24R,25(OH)2-vitamin D3 is essential for normal insulin secretion in the perfused rat pancreas.
abstract: It has previously been shown that vitamin D deficiency impairs arginine-induced insulin secretion from the isolated, perfused rat pancreas (Science 1980; 209:823-25). Since vitamin D is known to be metabolized to 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) and 24R,25-dihydroxyvitamin D3 (24,25[OH]2D3), it is essential to clarify which vitamin D metabolite has the important role of enhancing insulin secretion. In this report, a comparison is made of the relative efficacy of 3-wk repletion with vitamin D3 (980 pmol/day), 1,25(OH)2D3 (39 pmol/day or 195 pmol/day), and 24,25(OH)2D3 (650 pmol/day) on arginine-induced insulin secretion from the isolated, perfused rat pancreas; in this experiment, the daily caloric intake of the animals receiving vitamin D or its metabolites was controlled by pair feeding to the caloric intake of the vitamin D-deficient rats. 1,25(OH)2D3 repletion was found to completely restore insulin secretion to the levels seen in vitamin D3-replete, pair-fed controls in both the first and second phases, while 24R,25(OH)2D3 only partially improved insulin secretion, and then only in the first phase. Changes of both serum calcium levels and dietary caloric intake after vitamin D metabolite administration are concluded to play a lesser role on the enhancement of insulin secretion, since, in a separate experiment, vitamin D-deficient rats with normal serum calcium levels did not show recovery of insulin secretion equivalent to the vitamin D-replete animals under conditions of dietary pair feeding. These results suggest that 1,25(OH)2D3 but not 24,25(OH)2D3 plays an essential role in the normal insulin secretion irrespective of the dietary caloric intake and prevailing serum calcium levels.
authors.forename: S
authors.initials: S
authors.lastname: Kadowaki
authors.forename: A W
authors.initials: AW
authors.lastname: Norman
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001835:Body Weight; D002117:Calcitriol / Q000502:physiology*; D002118:Calcium / Q000097:blood; D002762:Cholecalciferol / Q000502:physiology; D004100:Dihydroxycholecalciferols / Q000502:physiology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D014808:Vitamin D Deficiency / Q000503:physiopathology
chemical_list: D004100:Dihydroxycholecalciferols; D007328:Insulin; D002762:Cholecalciferol; D015650:24,25-Dihydroxyvitamin D 3; D001120:Arginine; D002117:Calcitriol; D002118:Calcium