1,25-Dihydroxyvitamin D3 enhances the effect of refeeding on steady state preproinsulin messenger ribonucleic acid levels in rats

• Published in: Endocrinology (Philadelphia) Vol. 126; no. 4; p. 2041
• Main Authors: Ozono, K, Seino, Y, Yano, H, Yamaoka, K
• Format: Journal Article
• Language: English
• Published: United States 01.04.1990
• Subjects: Animals; Calcitriol - pharmacology; Calcium - blood; Fasting; Homeostasis; Hydroxycholecalciferols - blood; Insulin - blood; Male; Proinsulin - genetics; Protein Precursors - genetics; Rats; Rats, Inbred Strains; RNA, Messenger - metabolism; Vitamin D Deficiency - blood; Vitamin D Deficiency - metabolism
• ISSN: 0013-7227
• DOI: 10.1210/endo-126-4-2041

To elucidate the regulatory mechanism of vitamin D action on insulin biosynthesis and secretion, we examined preproinsulin (ppI) mRNA levels in the pancreas of normal rats, vitamin D-deficient rats, and rats supplemented with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or calcium (Ca) for 3 days. The ppI mRNA levels determined by dot blot analysis in vitamin D-deficient, 1,25-(OH)2D3-replete, and Ca-replete rats were 39.1%, 68.7%, and 66.7%, respectively, of values in normal rats. These results concur with previously reported levels of insulin secretion in the perfused rat pancreas. The reduced level of ppI mRNA should lead to a decrease in insulin biosynthesis and, thus, impair insulin secretion in vitamin D-deficient rats. The observed partial recovery of ppI mRNA levels through supplementation of 1,25-(OH)2D3 or Ca may be one mechanism by which insulin secretion is restored in rats after 1,25-(OH)2D3 or Ca repletion. We examined further the time course of ppI mRNA accumulation in rats after a single administration of 1,25-(OH)2D3. When fasting was continued for an additional 24-h period after an overnight fast, ppI mRNA levels were not changed significantly in either vitamin D-deficient or replete rats. However, in the rats that were pair-fed after overnight fasting, ppI mRNA levels in 1,25-(OH)2D3-replete rats increased at 8 and 24 h, whereas ppI mRNA in vitamin D-deficient rats increased only at 24 h. Moreover, the increment at 24 h was significantly larger in 1,25-(OH)2D3-replete rats than in vitamin D-deficient rats. We conclude that 1,25-(OH)2D3 enhances steady state levels of ppI mRNA only under conditions of refeeding and during feeding.