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 (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.
Ozono
K
K
Department of Pediatrics, Osaka University School of Medicine, Japan.
Seino
Y
Y
Yano
H
H
Yamaoka
K
K
Seino
Y
Y
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D005215:Fasting; D006706:Homeostasis; D006887:Hydroxycholecalciferols / Q000097:blood; D007328:Insulin / Q000097:blood; D008297:Male; D011384:Proinsulin / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014808:Vitamin D Deficiency / Q000097:blood / Q000378:metabolism
D006887:Hydroxycholecalciferols; D007328:Insulin; D011498:Protein Precursors; D012333:RNA, Messenger; C013737:preproinsulin; D011384:Proinsulin; D002117:Calcitriol; D002118:Calcium