Effect of duration of insulin deficiency on membrane-bound and free ribosomes from livers of diabetic rats.

In order to define the effect of duration of diabetes on hepatic protein sysntesis, membrane-bound and free ribosomes were isolated from livers of rats, 3, 7 and 28 days after administration of intravenous streptozotocin (75 mg/kg). Hepatocytes from the same rats were subjected to ultrastructural quantitative analysis. By day 3 there was a significant loss in the amount of rough endoplasmic reticulum (RER) per volume cytoplasm; however, the normal ratio of membrane-bound ribosomes per unit length of membrane was maintained. These hepatocyte ultrastructural changes continued over the ensuing four weeks. In spite of this decrease in amount of RER, in vitro protein synthetic activity of hepatic membrane-bound polyribosomes was unchanged from controls at three days, and by 28 days protein synthetic activity of bound hepatic ribosomes from diabetic rats was almost twice that of normal controls (p less than .01). In contrast to the effect of diabetes on bound ribosomes, there was no change in protein synthetic activity of free polyribosomes isolated from livers of rats, 3, 7 or 28 days after induction of diabetes. Thus, the effect of any given degree of diabetes on hepatic protein synthesis appears to vary with the population of hepatic ribosomes being studied, and with duration of insulin deficiency.