Insulin-induced renal dysfunction in regular Sabra rats.
1. We tested the effects of chronic hyperinsulinaemia on renal function. Hyperinsulinaemia, in the range of 1.5-4 times the control levels, was achieved using a sustained-release insulin implant. Sham-treated rats served as controls. 2. Experiment 1. Acute saline loading: seven sham and seven hyperinsulinaemic rats received an acute saline load (4 mL/100 g). Two h post-load urea and creatinine excretion rats were (mu mol/min) 15 +/- 5 and 9 +/- 4, and 0.17 +/- 0.05 and 0.10 +/- 0.04, respectively; P < 0.05 for both. 3. Experiment 2. Chronic saline loading: 12 sham- and 24 insulin-treated rats drank saline for 8 weeks plus 4% NaCl in the food for 2 more weeks. By week 10 plasma creatinine (mu mol/L) was 62 +/- 12 and 78 +/- 13, and creatinine clearance (mL/min) was 1.9 +/- 0.5 and 1.5 +/- 0.4, respectively; P < 0.05 for both. 4. Experiment 3. Regular diet: 10 sham- and 14 insulin-treated rats had, by week 8, plasma creatinine (mu mol/L) of 75 +/- 34 and 96 +/- 37 and creatinine clearance (mL/min) of 1.260 +/- 0.025 and 0.97 +/- 0.22, respectively; P < 0.02 for both. Bodyweight, resting blood pressure and urinary Na+ and K+ excretion were comparable in sham- and insulin-treated rats. 5. In three experimental settings long-term hyperinsulinaemia was associated with a subtle but significant renal dysfunction. This finding may be related to the aetiology of renal complications of hypertension and diabetes mellitus, both of which are insulin-resistant and hyperinsulinaemic states.
Bursztyn
M
M
Hypertension Unit, Department of Medicine, Hadassah University Hospital, Mount Scopus, Israel.
Ben-Ishay
D
D
Mekler
J
J
Raz
I
I
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003401:Creatine / Q000097:blood; D006946:Hyperinsulinism / Q000150:complications / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000633:toxicity*; D007328:Insulin / Q000097:blood / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology; D007677:Kidney Function Tests; D051381:Rats
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D003401:Creatine