Modulation of kidney cell protein degradation by insulin

Insulin is an established regulator of intracellular proteolysis in several mammalian tissues but little is known about its role in the kidney. The present study was undertaken to determine whether insulin influences protein degradation in isolated rat renal proximal tubules and to investigate its mechanism of action in cultured proximal-like tubular epithelial cells from the opossum kidney. Long-lived protein degradation was determined from the release of carbon 14-labeled valine from previously labeled cellular protein under conditions designed to minimize label reutilization. In isolated tubules, the mean control rate of proteolysis was 2.18% per hour, indicating an appreciable turnover of cellular protein. Insulin (10(-6) mol/L) decreased the rate by 23%. In cultured kidney cells, the rate of protein degradation averaged 1.25% per hour in the presence of serum and 1.68% per hour in its absence, an increase of 34%. High insulin concentrations suppressed this acceleration completely, and physiologic levels inhibited it partially. No evidence was obtained to indicate that insulin action is mediated through stimulation of Na(+)-H+ antiport or through increased amino acid utilization. Ammonium chloride, however, strongly attenuated the serum deprivation response and the inhibitory effect of insulin. The exact mechanisms whereby insulin inhibits proteolysis is not known, but these findings are consistent with an inhibitory action of insulin on the lysosomal pathway.