INSULIN‐INDUCED RENAL DYSFUNCTION IN REGULAR SABRA RATS

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Abstract
Summary: 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 (4mL/100g). Two h post‐load urea and creatinine excretion rats were (μmol/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 (μmol/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 (μmol/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.