title: Insulin reverses the protection given by diabetes against gentamicin nephrotoxicity in the rat.
abstract: Rats with untreated diabetes mellitus are protected from gentamicin-induced 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 levels were successfully maintained under 126 mg/dl. To serve as the control group, eight age-matched diabetic (plasma glucose > 400 mg/dl) rats had miniosmotic pumps placed delivering only Ringer's solution. Six days after placement of the pumps, gentamicin (40 mg/Kg/day) was administered to all animals for 9 days. The insulin-treated diabetic rats exhibited clear signs of nephrotoxicity by Day 6 of gentamicin, whereas the diabetic control group remained free from any functional or morphological evidence of proximal tubular damage throughout the 9 days of the aminoglycoside administration. At the end of the experiment, the creatinine clearance in the insulin-treated diabetic group was 45% lower than in the untreated diabetic group (P < 0.005). In addition, there was a rise in plasma creatinine (P < 0.02), muramidase appeared in the urine, and mild patchy acute tubular necrosis of the renal cortex was observed by light microscopic examination. The insulin-treated group also accumulated more gentamicin in the renal cortex than the untreated animals (P < 0.005). It is concluded that protection against the nephrotoxic 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.
authors.affiliation: Research Service, Veterans Affairs Medical Center, Miami, Florida 33125.
authors.forename: W
authors.initials: W
authors.lastname: Gouvea
authors.forename: D
authors.initials: D
authors.lastname: Roth
authors.forename: H
authors.initials: H
authors.lastname: Alpert
authors.forename: J
authors.initials: J
authors.lastname: Kelley
authors.forename: V
authors.initials: V
authors.lastname: Pardo
authors.forename: C A
authors.initials: CA
authors.lastname: Vaamonde
mesh_terms: D000818:Animals; D001835:Body Weight; D003401:Creatine / Q000097:blood / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D005839:Gentamicins / Q000032:analysis / Q000633:toxicity*; D006029:Glycosuria / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007672:Kidney Cortex / Q000737:chemistry / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000187:drug effects*; D011141:Polyuria / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005839:Gentamicins; D007328:Insulin; D003401:Creatine