Insulin prophylaxis down-regulates islet antigen expression and islet autoimmunity in the low-dose Stz mouse model of diabetes.
The aims of this study were to evaluate in an autoimmune diabetes animal model [low-dose streptozotocin (LD-STZ) mouse] (a) the efficacy of a prophylactic insulin treatment as a diabetes prevention tool, and (b) its possible mechanisms through both the insulitis evaluation and islets antigen expression. Diabetes was induced in male C57Bl6/J mice with STZ (50 mg/kg b/w for five consecutive days); insulin (1 U/day) was injected subcutaneously for ten consecutive days before the induction of diabetes and for a further ten days. Seventy-one male C57Bl6/J mice were grouped as follows: Group 1 (n = 25) made diabetic with i.p. STZ, Group 2 (n = 21) made diabetic with i.p. STZ and injected subcutaneously with insulin, Group 3 (n = 15) injected with insulin, while Group 4 (n = 10) comprised normal animals as controls. The animals of each group were killed at two intervals: half of them at day 12 and the remainder at day 24 from the beginning of the STZ treatment. A significant reduction of glycemia levels and insulitis severity was observed between mice of Group 1 vs. Group 2 at day 12 and day 24. Down-regulation of islet antigen expression (insulin, A2B5, GM2-1, ICA Ag) was achieved even without a complete metabolic suppression of beta-cell activity. In conclusion, prophylactic insulin treatment is effective to reduce glycemia levels and insulitis severity and down-regulates islet antigen expression in the LD-STZ model.
Anastasi
E
E
Endocrinology, Clinica Medica 2, University of Rome La Sapienza, Italy.
Dotta
F
F
Tiberti
C
C
Vecci
E
E
Ponte
E
E
Di Mario
U
U
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D015536:Down-Regulation; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage*; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013311:Streptozocin
D001324:Autoantigens; D007328:Insulin; D013311:Streptozocin