Protein turnover in insulin-treated, alloxan-diabetic lean and obese Zucker rats.
Obese and lean Zucker rats were made diabetic by intracardiac injections of alloxan (65-72 mg/kg body weight) and then given daily injections of protamine zinc insulin [1.25 U/(100 g/d)] for 6, 9 and 12 d. Body weight, food intake, plasma glucose and immunoreactive insulin concentrations were not different for lean and obese diabetic rats of similar ages. Rates of increase in carcass protein, mixed muscle protein and myofibrillar protein were less in obese than in lean rats. However, rates of increase for the sarcoplasmic fraction were not different. Fractional rates of synthesis of total muscle protein and myofibrillar protein, as determined by continuous intravenous infusion of [14C]tyrosine, were comparable in the two genotypes. Fractional rate of myofibrillar protein degradation, as determined by urinary 3-methylhistidine excretion, was higher in obese than in lean rats. Differences in calculated absolute rates between genotypes did not parallel differences in the fractional rates, due mainly to a smaller protein mass in obese rats. As a consequence, absolute synthetic rates were lower in obese rats, while absolute degradation rates were similar in the two genotypes. In contrast, rates of liver protein synthesis were similar in obese and lean rats, whether expressed as fractional or absolute rates. These results indicate that decreased protein deposition in the obese animal is a consequence of both an absolute decrease in protein synthesis in muscle as well as a disproportionately elevated protein degradation in muscle. Hyperinsulinemia normally seen in obese rats may be an adaptive response to minimize the impaired balance between protein synthesis and degradation.
D000818:Animals; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D007328:Insulin / Q000627:therapeutic use; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008762:Methylhistidines / Q000378:metabolism; D024510:Muscle Development; D009124:Muscle Proteins / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D007328:Insulin; D008762:Methylhistidines; D009124:Muscle Proteins; D011506:Proteins; D014443:Tyrosine; C028118:3-methylhistidine; D009584:Nitrogen