PROTEIN-TURNOVER IN SKELETAL-MUSCLE OF THE DIABETIC RAT - ACTIVATION OF UBIQUITIN-DEPENDENT PROTEOLYSIS

Induction of experimental insulin-deficiency by a single administratio n of streptozotocin to rats resulted in substantial changes in heart a nd skeletal muscle size and protein content. This was accompanied by a marked loss of total body (carcass) nitrogen and raised concentration s of circulating branched-chain amino acids. These changes were relate d to alterations in protein turnover in skeletal muscle. Thus, the dia betic animals showed changes in both the fractional protein rates of s ynthesis (decreased by 37%) and degradation (increased by 141%). The i ncreased protein degradation observed in the muscle of the diabetic an imals was associated only with an increase in the expression of the ge nes controlling ubiquitin-dependent proteolysis. It may be suggested t hat the hormonal changes associated with the diabetic state play an im portant role in the regulation of the activity of the ubiquitin-depend ent proteolytic system in skeletal muscle, highlighting the major role of this system in the diabetes-related cachexia.