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)₂D₃but 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.