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.
| Original language | English |
|---|---|
| Pages (from-to) | 445-453 |
| Number of pages | 9 |
| Journal | Proceedings of the Society for Experimental Biology and Medicine |
| Volume | 206 |
| Issue number | 4 |
| State | Published - Jan 1 1994 |
Fingerprint
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Insulin reverses the protection given by diabetes against gentamicin nephrotoxicity in the rat. / Gouvea, W.; Roth, David; Alpert, H.; Kelley, J.; Pardo, V.; Vaamonde, C. A.
In: Proceedings of the Society for Experimental Biology and Medicine, Vol. 206, No. 4, 01.01.1994, p. 445-453.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Insulin reverses the protection given by diabetes against gentamicin nephrotoxicity in the rat
AU - Gouvea, W.
AU - Roth, David
AU - Alpert, H.
AU - Kelley, J.
AU - Pardo, V.
AU - Vaamonde, C. A.
PY - 1994/1/1
Y1 - 1994/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0028071839&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028071839&partnerID=8YFLogxK
M3 - Article
C2 - 8073055
AN - SCOPUS:0028071839
VL - 206
SP - 445
EP - 453
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
SN - 0037-9727
IS - 4
ER -