Role of different proteolytic pathways in degradation of muscle protein from streptozotocin-diabetic rats

In vitro rates of overall proteolysis and the activities of four different proteolytic pathways (lysosomal, Ca2+ dependent, ATP dependent, and ATP independent), as well as rates of protein synthesis, were measured in soleus and extensor digitorum longus (EDL) muscles from streptozotocin- diabetic rats. In the acute phase (1-3 days) of diabetes, there was an increase in overall proteolysis that coincided with an increased activity of the Ca2+-dependent pathway in both soleus and EDL and of the ATP-dependent pathway in EDL. After longer periods (5-10 days) of diabetes, the overall rate of protein degradation decreased and reached values similar to or even lower than those of controls as a result of a reduction in the activities of Ca2+-dependent and ATP-dependent pathways. No change was detected at any time interval in the activity of the intralysosomal proteolytic system in muscles from diabetic animals. Rates of protein synthesis were already reduced 24 h after diabetes induction and decreased further thereafter. Insulin treatment restored to normal the activities of the proteolytic pathways and rates of protein synthesis.

Keywords

adenosine triphosphate-dependent proteolysis, calcium-dependent proteolysis, lysosomal proteolysis, protein synthesis, adenosine triphosphate, calcium ion, calpain, cycloheximide, fatty acid, insulin, lysosome enzyme, muscle protein, phenylalanine, animal model, animal tissue, body weight, controlled study, enzyme activity, extensor digitorum longus muscle, fatty acid blood level, glucose blood level, insulin treatment, male, muscle mass, nonhuman, priority journal, protein degradation, rat, soleus muscle, streptozocin diabetes, Adenosine Triphosphate, Animals, Blood Glucose, Body Weight, Calcium, Diabetes Mellitus, Experimental, Fatty Acids, Nonesterified, Insulin, Lysosomes, Male, Muscle Proteins, Muscles, Organ Size, Peptide Hydrolases, Rats, Rats, Wistar