AJP - Endocrinology and Metabolism, Vol 263, Issue 5 E856-E862, Copyright © 1992 by American Physiological Society
Effects of streptozotocin-induced diabetes on rough endoplasmic reticulum and lysosomes of rat liver
S. E. Lenk, D. Bhat, W. Blakeney and W. A. Dunn Jr
Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville 32610-0235.
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.
