An experimental study was designed to test a drug candidate for the treatment of diabetes mellitus in rats with streptozotocin (STZ) diabetes.
Diabetes was induced in outbred male rats (280300 g) by single iv injection of streptozotocin 50 mg/kg. The animals showing hyperglycemia (1215 mM) 72 hours after injection were randomized to receive daily intragastric doses of distilled water, glibenclamid 8 mg/kg, or polyclonal antibodies to C-terminal fragment of insulin receptor, beta subunit (ultra-low doses, anti-InsR); the last group received insulin subcutaneously (12 U/kg). For 7 weeks, the animals were monitored for fasting glycemia, glycosuria, and glucose tolerance.
STZ caused a sustained hyperglycemia (1221 mM versus 2.33.2 in intact rats, maximum at day 42) and glycosuria (2.73.7 mM versus 0.81.8 mM in intact rats). Glucose tolerance reduced 3.55.5-fold (calculated by AUC in glucose load test). The rats featured polydipsia (an 2.73.2-fold increase in water consumption), body weight reduced by 50%. Due to diabetes and its complications, survival rate reduced to 12.5% (from 100% in intact rats).
Glycemia reduced by 3050% in insulin group, and by 1042% glibenclamid group, though remained abnormal. STZ-induced glycosuria remained unaffected in both groups. Survival rate increased up to 20%. Peroral anti-InsR was much more effective in reduction of glycemia (to normal values, 5.03.0 mM) and glycosuria (below 0.8 mM). Anti-InsR enhanced survival to 30%. The increase in glucose tolerance was most considerable in insulin and anti-InsR groups, less marked in glibenclamid group.
The peroral anti-InsR agent is regarded as a promising candidate therapeutic for the treatment of diabetes mellitus.