INSULIN REVERSES THE PROTECTION GIVEN BY DIABETES AGAINST GENTAMICIN-NEPHROTOXICITY IN THE RAT

Rats with untreated diabetes mellitus are protected from gentamicin-in duced nephrotoxicity. In order to evaluate the role of hyperglycemia, glycosuria, and polyuria in this phenomenon, miniosmotic pumps filled with insulin were implanted for 15 days in seven female Sprague-Dawley rats with streptozotocin-induced diabetes mellitus. Plasma glucose le vels were successfully maintained under 126 mg/dl. To serve as the con trol group, eight age-matched diabetic (plasma glucose >400 mg/dl) rat s had miniosmotic pumps placed delivering only Ringer's solution. Six days after placement of the pumps, gentamicin (40 mg/Kg/day) was admin istered to all animals for 9 days. The insulin-treated diabetic rats e xhibited clear signs of nephrotoxicity by Day 6 of gentamicin, whereas the diabetic control group remained free from any functional or morph ological evidence of proximal tubular damage throughout the 9 days of the aminoglycoside administration. At the end of the experiment, the c reatinine clearance in the insulin-treated diabetic group was 45% lowe r than in the untreated diabetic group (P < 0.005). In addition, there was a rise in plasma creatinine (P < 0.02), muramidase appeared in th e urine, and mild patchy acute tubular necrosis of the renal cortex wa s observed by light microscopic examination. The insulin-treated group also accumulated more gentamicin in the renal cortex than the untreat ed animals (P < 0.005). It is concluded that protection against the ne phrotoxic effects of gentamicin is a feature of untreated experimental diabetes mellitus in the rat and that correction of the hyperglycemic state with insulin reverses this resistance.