The de novo synthesis of numerous proteins is decreased during vitamin D3 deficiency and is gradually restored by 1, 25-dihydroxyvitamin D3 repletion in the islets of langerhans of rats

Abstract

Since both the release and de novo biosynthesis of insulin are severely decreased by vitamin D 3 deficiency and improved by 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) repletion following a 6-h delay in the rat, the present experiments investigated the effects of vitamin D 3 deficiency on the biosynthesis of heavier molecular weight proteins using electrophoretic separation. Gel protein staining by Coomassie blue showed very different profiles for islets protein production from 4-week vitamin D 3 -deficient rats compared with normal islets. The pattern was characterised by a decrease in high molecular weight proteins, concomitantly accompanied by an increase in low molecular weight proteins. This tendency was partially reversed in vivo by 1,25(OH) 2 D 3 repletion treatment for 7 days and was evident after only 16 h of treatment.In parallel with these in vivo observations, which represent a static index of islets protein production, a kinetic study was performed in vitro by a double-labelling method allowing us to measure the de novo synthesis of proteins in islets during a strong 16·7 mM glucose stimulation. Comparison of 3 H and 14 C labelled samples was achieved via coelectrophoresis to avoid experimental artefacts. The study of the ratio of d.p.m.3 H/d.p.m. 14 C for each molecular weight protein in islets stimulated by 16·7 mM glucose (versus basal 4·2 mM glucose) showed an increase in the height of certain peaks: 150, 130 and 8·5 kDa.Under the same conditions, islets from 4-week vitamin D 3 -deficient rats (versus normal islets) presented a large deficit of numerous newly synthesised proteins and particularly those implicated in the response to glucose stimulation. In vitro repletion of 1,25(OH) 2 D 3 tended to reverse, at least in part, the deleterious effect of vitamin D 3 deficiency on the de novo protein synthesis of islets but these effects were gradual. Indeed, there was no detectable effect at 2 h incubation, but 1,25(OH) 2 D 3 increased the 60 to 65 kDa, 55 kDa, and 9 to 8 kDa molecular mass proteins at 4 h, and increased the level of most newly synthesised proteins at 6 h. These data support the hypothesis of a beneficial genomic influence of 1,25(OH) 2 D 3 that occurs progressively within the islets of Langerhans and which may prepare the cells for an enhanced response to glucose stimulation.

Association of vitamin D deficiency with incidence of type 2 diabetes in high-risk Asian subjects

“…There is ample evidence in in vitro and in vivo studies showing that vitamin D activity is essential for pancreatic b cell function (34)(35)(36). In our study, the circulating concentration of 25(OH)D was positively associated with IGI, which reflects acute phase insulin secretion; however, the correlation was weak (r = 0.077, P , 0.05).…”

Vitamin D and its Relation with Insulin Resistance in Obese Children

“…[25] Insulin release mechanism and glucose homeostasis are influenced by vitamin D. Earlier reports suggest that decrease of vitamin D may alter the glucose homeostasis. [26][27][28] However, role of vitamin D in children is still unclear. Various studies suggested that decrease vitamin D level is increased insulin resistance in adults.…”

Vitamin D Deficiency: A New Risk Factor for Type 2 Diabetes

“…Vitamin D was reported to be essential for insulin secretion from pancreatic β-cells [8] in both in vitro and in vivo studies [91,92,93]. The mechanisms by which vitamin D acts on insulin secretion are thought to be both direct and indirect [14]; in particular, the direct effect of vitamin D on insulin synthesis and secretion is suggested by the demonstrated binding of the active form 1,25(OH)D to the vitamin D receptor on β-cells, by the identification of vitamin D response elements in the human insulin gene promoter [94], and by the transcriptional activation of the human insulin gene caused by 1,25(OH)D [95].…”