Effects of a vitamin D3 analog on diabetes in the bio breeding (BB) rat.
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.
Pedullà
Marcella
M
Dipartimento di Pediatria, Seconda Università degli Studi di Napoli, Italy.
Desiderio
Vincenzo
V
Graziano
Antonio
A
d'Aquino
Riccardo
R
Puca
Andrew
A
Papaccio
Gianpaolo
G
D000818:Animals; D002118:Calcium / Q000097:blood / Q000652:urine; D002762:Cholecalciferol / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB
D002762:Cholecalciferol; D002118:Calcium