Effects of a vitamin D₃ analog on diabetes in the bio breeding (BB) rat

Abstract

Non-hypercalcemic analogs of vitamin D(3) modulate the immune response through antigen-presenting cells (APCs) and activated T-cells. A large population-base case-control showed that vitamin D(3) intake significantly decreases the risk of type 1 diabetes development. The aim of this study was, therefore, to observe the in vivo effects of a vitamin D(3) analog administered to Bio Breeding (BB) rats. 1,25-Dihydroxy-16,23Z-diene-26,27-hexafluoro-19-nor vitamin D(3) (BXL-219, formerly Ro 26-2198) (BioXell, Milan, Italy) was administered in vivo to BB rats from days 42 to 110 of life at 0.2 microg/Kg BW. Control animals received only vehicle (olive oil, 4.8 microl/100 g BW). The animals of these two groups were subjected to insulin treatment as they became diabetic. Insulin (Humulin, 28.6 UI/day) was administered irrespective of diabetes occurrence to another group of rats for comparison. Blood glucose, insulin levels, glycosuria, degree of islet infiltration, and the expression of some antigens were observed. Results showed that the vitamin D(3) analog reduced diabetes incidence, although limitedly, in BB rats while administration of oral insulin increased diabetes incidence. In addition, the vitamin D(3) analog did not stimulate an enhancement in the expression of CD4 and CD25 in BB rats as it does in NOD mice, which may explain the failure of this as well as other antidiabetic treatments in the BB animal model of type 1 diabetes.

No association of vitamin D intake or 25-hydroxyvitamin D levels in childhood with risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY)

“…Mechanistically, vitamin D has been shown to shift the balance of the body’s T cell response towards down-regulation of the Th1 immune response [2]. Both in vitro studies and animal studies have found that vitamin D stimulates a Th2 response [3–5]. …”

Vitamin D and Diabetes

“…Interestingly, several of the vitamin D analogs possess more potent immunomodulatory properties, resulting in protection against autoimmunity and prolongation of allograft survival [104,125e127]. Some of the most promising analogs coming from different chemical laboratories have been tested in the NOD mouse [125] as well as in the BB rat [128]. The mechanism of protection against insulitis and diabetes appears to be similar to that of the mother compound, 1,25(OH) 2 D 3 .…”

Preventing Bone Loss and Weight Gain with Combinations of Vitamin D and Phytochemicals

“…Other investigators reported that a vitamin D 3 analog reduced diabetes incidence in rats that received 0.2 lg/kg of body weight. 42 A dose of genistein at 1,500 mg/kg of feed, when administered to ovariectomized female mice, caused weight loss and adipose tissue apoptosis. 10,43 Quercetin at 2.5% of the diet increased bone density of both the lumbar spine and femur in ovariectomized female mice.…”