The effect of experimental diabetes mellitus and insulin replacement on hepatic ultrastructure and protein synthesis

The following study was conducted in order to define the specific alterations in hepatic ultrastructure responsible for the decrease in hepatic protein synthesis associated with experimental diabetes. Rats received intravenous alloxan (70 mg/kg) and 48 h later were either sacrificed or given insulin for 1, 2, 4, 6, or 24 h. Specimens for electron microscopic evaluation and morphometric analysis were taken from the same livers used to isolate ribosomes for measurement of in vitro protein synthesis. Our results show that hepatocytes from animals with untreated alloxan diabetes show varying degrees of disorganization and loss of rough endoplasmic reticulum (RER) which is directly related to the severity of the alloxan diabetes. A significant correlation existed between the severity of ultrastructural changes as judged by the loss of both membrane and polysome components of the RER and degree of inhibition of protein synthesis (P < 0.001). Abnormalities of hepatic ultrastructure and protein synthesis were reversed within 24 h of insulin administration. The data are consistent with the view that it is the relative decrease in hepatic polysomes that results from the loss of RER in alloxan diabetes that is responsible for the decrease in hepatic protein synthesis.