Protein synthesis in a postmitochondrial supernatant system from rat liver. An effect of diabetes at the level of peptide chain initiation

Hepatic ribosome preparations from diabetic rats have a lower polysome content than those from normal animals, and show reduced protein synthetic activity in cell-free systems [l-4]. More detailed analysis of the effects of diabetes has been carried out with skeletal muscle, in which similar, but more pronounced, changes occur [S], and it seems likely that in this tissue insulin exerts translational control on protein synthesis at the level of peptide chain initiation [6, 71. In the studies with liver [l-4], the cell-free systems which were used consisted of recombined ribosome and cell sap fractions. In such systems, most of the amino acid incorporation obtained represents elongation of existing nascent peptide chains, and the extent of initiation of new chains is small [8]. However, crude hepatic postmitochondrial supematants (PMS)* are twice as active in amino acid incorporation as more highly fractionated systems [9], and the ribosomes in the crude system show some ability to re-initiate on to endogenous mRNA [ 10-121. The data in the present report show that PMS preparations from livers of diabetic rats show a reduced ability to incorporate amino acids into protein. This difference between extracts from diabetic and control animals is almost completely abblished in the presence of inhibitors of peptide chain initiation.