Effects of streptozotocin-induced diabetes on rough endoplasmic reticulum and lysosomes of rat liver.

Abstract

In the absence of amino acids and insulin, ribosome-free regions of the rough endoplasmic reticulum (RER) invaginate to form an autophagosome, which matures into an autolysosome (W. A. Dunn, Jr., J. Cell Biol. 110: 1923-1933, 1990). In this study, biochemical and morphological methods were used to examine the structure and integrity of the RER and the lysosome-vacuolar system in livers of untreated (normal serum insulin) and streptozotocin (STZ)-treated (depressed serum insulin) fed and fasted rats. Degradation of endogenous proteins was increased by 70% in STZ-treated animals. Proteolysis was further enhanced when these animals were deprived of food for 24 h. These alterations in protein turnover were accompanied by increases in the fractional volume of autophagic vacuoles and in the hepatic amounts of three lysosomal hydrolases. These effects of STZ were prevented on administration of insulin. In addition, there was an insulin-dependent 50% loss of RER surface area in livers from STZ-treated rats. This loss of structural RER was accompanied by comparable decreases in the cellular amounts of two RER membrane proteins and one luminal protein, suggesting that the RER was degraded as a unit. Additional losses of RER were observed when STZ-treated rats were fasted. Furthermore, the hepatic amounts of two serum proteins decreased, suggesting the functional capacity of the RER was reduced. Combined, the data suggest that in STZ-induced diabetes the losses in RER are related to enhanced autophagy.