Divergent Effects of Unilateral and Subtotal Nephrectomy on Insulin Sensitivity in Rats

Abstract

Objectives. Insulin resistance is associated with chronic renal failure, which may amplify its cardiovascular pathologic manifestations. We previously showed the presence of insulin resistance in mild renal insufficiency due to chronic glomerulonephritis. These observations may be explained by a decrease in insulin sensitivity due to renal dysfunction. The aim of the present study was to evaluate the effects of unilateral and subtotal nephrectomy on insulin sensitivity. Methods. Unilateral heminephrectomy and five-sixths nephrectomy (5/6Nx) were performed in male Sprague–Dawley rats, measuring steady-state plasma glucose (SSPG) during the insulin suppression test. Results. The glomerular filtration rate (GFR) decreased significantly from sham-operated rats, to unilateral heminephrectomy group, to 5/6Nx rats. SSPG was unexpectedly lower in the unilateral heminephrectomy group than in controls, suggesting that unilateral heminephrectomy increased the sensitivity to insulin despite a mild decrease in renal function. However, when the analysis was limited to the 5/6Nx group, SSPG was inversely correlated with GFR (r = − 0.65, p < 0.05). When renal failure caused by 5/6Nx had reached end stage, the rats became insulin resistant, despite a profound reduction in renal mass. Conclusion. It is suggested that unilateral heminephrectomy reduced GFR and increased the sensitivity to insulin. When rats became uremic, insulin sensitivity decreased, even, in 5/6Nx.

• insulin resistance
• steady-state plasma glucose
• nephrectomy
• end-stage renal disease
• gluconeogenesis