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Published on: August 14, 2013
Effects of a vitamin D3 analog on diabetes in the bio breeding (BB) rat
Marcella Pedullà1, Vincenzo Desiderio, Antonio Graziano
1Dipartimento di Pediatria, Seconda Università degli Studi di Napoli, Italy.
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.
Insights
A vitamin D(3) analog showed a limited reduction in type 1 diabetes incidence in Bio Breeding rats. Oral insulin administration, however, increased diabetes incidence in this animal model.
Area of Science:
- Immunology
- Endocrinology
- Metabolic diseases
Background:
- Non-hypercalcemic vitamin D(3) analogs modulate immune cells like antigen-presenting cells (APCs) and T-cells.
- Vitamin D(3) intake is associated with a decreased risk of type 1 diabetes development.
- The Bio Breeding (BB) rat is an established animal model for type 1 diabetes.
Purpose of the Study:
- To investigate the in vivo effects of a vitamin D(3) analog (BXL-219) in BB rats.
- To assess the analog's impact on diabetes incidence and related biomarkers.
- To compare the effects of the vitamin D(3) analog with insulin treatment in BB rats.
Main Methods:
- Administration of 1,25-Dihydroxy-16,23Z-diene-26,27-hexafluoro-19-nor vitamin D(3) (BXL-219) to BB rats from day 42 to 110 of life.
- Control groups received vehicle or insulin treatment.
- Monitoring of blood glucose, insulin levels, glycosuria, islet infiltration, and antigen expression (CD4, CD25).
Main Results:
- The vitamin D(3) analog demonstrated a limited reduction in type 1 diabetes incidence in BB rats.
- Oral insulin administration was observed to increase diabetes incidence in the study population.
- The vitamin D(3) analog did not enhance CD4 and CD25 expression in BB rats, unlike in NOD mice.
Conclusions:
- The vitamin D(3) analog BXL-219 exhibits a modest protective effect against type 1 diabetes in BB rats.
- The differential immune response in BB rats compared to NOD mice may explain treatment efficacy variations.
- Further research is needed to understand the specific mechanisms underlying vitamin D(3) analog action in type 1 diabetes models.
