1,25-DIHYDROXYVITAMIN-D3 ENHANCES THE EFFECT OF REFEEDING ON STEADY-STATE PREPROINSULIN MESSENGER-RIBONUCLEIC-ACID LEVELS IN RATS

To elucidate the regulatory mechanism of vitamin D action on insulin biosynthesis and secretion, we examined preproinsulin (ppl) mRNA levels in the pancreas of normal rats, vitamin D-deficient rats, and rats supplemented with 1,25-dih-ydroxyvitamin D3[l,25-(OH)2D3] or calcium (Ca) for 3 days. The ppl mRNA levels determined by dot blot analysis in vitamin D-deficient, l,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 ppl mRNA should lead to a decrease in insulin biosynthesis and, thus, impair insulin secretion in vitamin D-deficient rats. The observed partial recovery of ppl mRNA levels through supplementation of l,25-(OH)2D3or Ca may be one mechanism by which insulin secretion is restored in rats after l,25-(OH)2D3or Ca repletion. We examined further the time course of ppl mRNA accumulation in rats after a single administration of l,25-(OH)2D3. When fasting was continued for an additional 24-h period after an overnight fast, ppl 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, ppl mRNA levels in l,25-(OH)2D3-replete rats increased at 8 and 24 h, whereas ppl mRNA in vitamin D-deficient rats increased only at 24 h. Moreover, the increment at 24 h was significantly larger in l,25-(OH)2D3-replete rats than in vitamin D-deficient rats. We conclude that l,25-(OH)2D3enhances steady state levels of ppl mRNA only under conditions of refeeding and during feeding. © 1990 by The Endocrine Society.