Effects of vitamin D deficiency and repletion on insulin and glucagon secretion in man

Abstract

Summary.We have studied the effects of vitamin D deficiency on pancreatic A-and B-cell function. Four subjects with vitamin D deficiency and 10 healthy subjects were studied. Pancreatic B-cell function was assessed by the insulin response to an oral glucose tolerance test. An insulin tolerance test was used to evaluate pancreatic A-cell function. The patients were then treated with 2000 U/day of vitamin D 3 for 6 months, after which the clinical, metabolic, biochemical and radiological features of vitamin D deficiency resolved, and pancreatic Aand B-cell function was repeated. In the vitamin D-deficient subjects pre-treatment and post-treatment serum calcium levels (mean _+ SEM) were 2.22+0.01mmol/1 and 2.24_+ 0.01 mmol/l respectively, and 2.27 _+ 0.02 mmol/l in healthy subjects (NS). The pre-treatment level of 1,25-dihydroxy vitamin D (1,25-(OH)2D) of 29.7 _+ 3.3 pg/ml in the vitamin D deficient subjects rose to 70.3 _+10.3 pg/ml after treatment (p < 0.05). The 1,25-(OH)2D level in the healthy subjects was 50.0 + 13.7 pg/ml (p < 0.05 versus pre-and post-treatment values in the patients). Insulin secretion, calculated by the area under the insulin curve, was significantly lower before vitamin D 3 treatment in the patients (9.09 + 0.7 mU x min, p<0.05) compared with the healthy subjects (11.9_+ 0.5 mU x min) and post-treatment values of the patients with vitamin D deficiency (13.7 + 0.5 mU x min). Similar changes were seen in the insulogenic indices (AI/AG). While AI/AG was 1.71 _+ 0.4 (mean + SEM) during vitamin D deficiency, it increased to 2.48_+0.3 with vitamin D repletion. The insulogenic index in the healthy subjects was 2.68 _+ 0.3. The glucose areas were not significantly different. Insulin-induced glucagon secretion was similar in all instances. The results of this study suggest that vitamin D deficiency reduces pancreatic insulin secretion but it does not affect pancreatic A-cell function.Key words: Vitamin D, insulin, glucagon secretion.Vitamin D is essential in higher animals and man for the maintenance of calcium and phosphorus homeostasis [1]. This is accomplished by the sequential metabolism of vitamin D by the liver and kidney into its principal biologically active metabolite, 1,25-dihydroxyvitamin D (1,25-(OH)2D) [2,3]. The effect of 1,25-(OH)2D has been associated with calcium and phosphate handling in intestine, bone and kidney. It has been established that 1,25-(OH)2D acts on these three tissues, as receptors for 1,25-(OH)2D have been found in these tissues [4][5][6]. Moreover, a large number of previously unrecognized target organs have been identified. Among them are stomach, skin, pituitary, brain and the endocrine pancreas [7][8]. Recent autoradiographic studies have provided evidence that 1,25-(OH)2D is selectively concentrated in and retained by pancreatic islet cells, suggesting a genomic action on B-cell function [8].Because of the known effects of vitamin D on membrane and calcium transport [9,10], abnormalities in vitamin D metabolism could alter endocrine cell membrane function and ...

Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice

“…As shown previously, severe rickets leads to decreased insulin synthesis, insulin secretion and even overt insulin deficiency in vivo [42,43,44]. In the present study islets isolated from vitamin D-deficient mice at 100 days of age had an insulin synthetic and secretory capacity comparable to islets from control NOD mice.…”

Vitamin D and diabetes

“…Vitamin D deficiency was linked to IGT and type 2 diabetes in humans many years ago [5,28]. These observations were confirmed in animal models, which demonstrated that pancreatic insulin secretion is inhibited by vitamin D deficiency [29].…”

“…The amount of vitamin D administered to these patients with rickets was, however, subject to wide variation (from the daily oral administration of 2,000 IU [28] to a single intramuscular injection of 100,000 IU [3]), making it difficult to draw clear conclusions and establish guidelines. Nonetheless, it is clear that vitamin D deficiency should be treated, and that improved glucose tolerance is a desirable side effect.…”

Pharmacokinetics and effects of demographic factors on blood 25(OH)D3 levels after a single orally administered high dose of vitamin D3

“…Epidemiological studies have suggested an inverse relationship between serum 25(OH)D3 levels and glucose levels [18][19][20] . However, the results of clinical trials studying the associations between vitamin D supplementation and blood glucose levels have been inconclusive [21][22][23][24] . Using meta-analysis methods, vitamin D interventions have been determined to have no significant effects on blood glucose levels for the general population, although they may have a small effect on fasting serum glucose levels for those with diabetes or impaired glucose tolerance [25] .…”