Effect of metformin treatment on glucose tolerance and glomerulosclerosis in KK mice.
Non-obese KK mice, aged 90-100 days, demonstrating an abnormal tolerance to glucose, hyperinsulinaemia with insulin resistance and glomerulosclerosis 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 their tolerance to the oral glucose load. A repeated oral glucose tolerance test at 16 weeks showed similar results. Blood lactate and insulin levels were similar in all 3 groups of mice. At sacrifice, responders had significantly less glomerulosclerosis compared to control mice. No difference in the incidence of glomerulosclerosis was found between control mice and non-responders. The data suggest that chronic metformin treatment improves glucose tolerance in 70% of KK mice without increasing blood lactate or insulin levels. This improvement in glycaemic control is associated with a lesser incidence of glomerulosclerosis in KK mice.
Department of Medicine, UMDNJ-New Jersey Medical School, Newark 07103.
A S
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Reddi
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Jyothirmayi
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology*; D007773:Lactates / Q000097:blood; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D007773:Lactates; D008687:Metformin