EFFECT OF METFORMIN TREATMENT ON GLUCOSE-TOLERANCE AND GLOMERULOSCLEROSIS IN KK MICE

Non-obese KK mice, aged 90-100 days, demonstrating an abnormal toleran ce to glucose, hyperinsulinaemia with insulin resistance and glomerulo sclerosis were treated with either water (control N=10) or metformin ( N=15), a biguanide, orally at a concentration of 50 mg/kg twice daily for 16 weeks. Oral glucose tolerance was performed at 7 weeks. Only 10 of 15 metformin-treated mice (responders) improved their oral glucose tolerance. The remaining 5 mice (non-responders) did not improve thei r tolerance to the oral glucose load. A repeated oral glucose toleranc e test at 16 weeks showed similar results. Blood lactate and insulin l evels were similar in all 3 groups of mice. At sacrifice, responders h ad significantly less glomerulosclerosis compared to control mice. No difference in the incidence of glomerulosclerosis was found between co ntrol mice and non-responders. The data suggest that chronic metformin treatment improves glucose tolerance in 70 % of KK mice without incre asing blood lactate or insulin levels. This improvement in glycaemic c ontrol is associated with a lesser incidence of glomerulosclerosis in KK mice.