ECE2007 Poster Presentations (1) (659 abstracts)
Oral antibodies to insulin receptor are found effective in the treatment of streptozotocin-induced diabetes in rats
Julia Dugina 1 , Andrey Martyushev-Poklad 1 , Irina Kheyfets 1 , Alexander Spasov 2 , Maria Samokhina 2 , Oleg Epstein 1 & Svetlana Sergeeva 1
1‘Materia Medica Holding’ Company, Moscow, Russia; 2Volgograd State Medica University, Volgograd, Russia.
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 (280–300 g) by single iv injection of streptozotocin 50 mg/kg. The animals showing hyperglycemia (12–15 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 (12–21 mM versus 2.3–3.2 in intact rats, maximum at day 42) and glycosuria (2.7–3.7 mM versus 0.8–1.8 mM in intact rats). Glucose tolerance reduced 3.5–5.5-fold (calculated by AUC in glucose load test). The rats featured polydipsia (an 2.7–3.2-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 30–50% in insulin group, and by 10–42% 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, 5.0–3.0 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.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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