Effect of Insulin Deficiency on Hepatic Ribosomal Aggregation

Ribosomes were isolated from liver homogenates of normal and alloxan diabetic rats. Sedimentation of these ribosomes through a continuous sucrose gradient indicated that insulin deficiency was associated with an increase in the proportion of ribosomes existing as the 80 S monomer. In a second series of experiments ribosomes from diabetic animals were also shown to bind more avidly to ³H-polyuridylic acid (polyU). When hepatic ribosomes from normal and diabetic rats were incubated for forty-five minutes at 37° C. in a complete amino acid-incorporating system they underwent essentially total disaggregation into single ribosomes, and the previously noted difference between normal and diabetic ribosome binding to polyU was abolished. The sedimentation characteristics of ribosomes from normal and diabetic rats indicate that insulin deficiency results in an increase in the proportion of ribosomes free of mRNA, and, since they are free of mRNA, a greater than normal proportion of ribosomes from diabetic animals are capable of complexing with polyU. Obviously, producing equal numbers of monosomes by prior incubation in an amino acid-incorporating system would be expected to obliterate the difference in polyU binding between ribosomes from normal and diabetic animals. Thus, both lines of experimental evidence are consistent with the hypothesis that insulin deficiency produces a disaggregation of hepatic poly-somes, leading to an increase in the proportion of ribosomes that are not bound to mRNA.