Renal protein degradation in streptozotocin diabetic mice.

In diabetes mellitus, the kidney and the gut--but not the liver or the muscle--undergo hypertrophy. Hypertrophy may be due to an increase in the rate of protein synthesis and/or to a decrease in proteolysis. In order to resolve this issue we assessed in vivo the rates of protein degradation by measuring the disappearance rates of 3H- and 14C-labelled valine incorporated into renal and liver proteins of control and streptozotocin-diabetic mice. The half-life of labelled valine, which is inversely related to the rate of protein degradation, was shorter and of similar magnitude both in the kidneys and livers of diabetic (70 +/- 6 h) than of control (96 +/- 8 h) animals. Yet, only the kidneys of diabetic animals underwent hypertrophy (0.33 +/- 0.01 vs. 0.29 +/- 0.01 g, P < 0.05; 2.22 +/- 0.10 vs. 1.64 +/- 0.05% of body weight, P < 0.01)). The increase in protein degradation rate affected all subcellular (mitochondrial, nuclear, microsomal and cytosolic) fractions of the kidney but not the mitochondria of liver. We surmise that an increase in the degradation of proteins is a widely generalized phenomenon in diabetes mellitus. For reasons that are still unclear, but that may relate to the hyperglycaemia, in the kidneys of diabetic animals this process is associated with a transiently larger increase in protein synthesis resulting in hypertrophy, whereas in liver, changes in protein degradation proceed 'pan passu' with those in protein synthesis resulting in the preservation of organ weight. Accelerated renal protein turnover and hypertrophy are early manifestations and perhaps harbingers of more severe renal changes in diabetes mellitus.