Muscle protein catabolism in diabetes: 3-methylhistidine excretion in the spontaneously diabetic "BB" rat.

The muscle protein lost in uncontrolled diabetes may be due to decreased synthesis, increased catabolism, or to any combination of alteration in these rates that results in net loss. Differing methods of examining these rates in vivo and in vitro have given conflicting results. We assessed the rate of catabolism of proteins containing 3-methylhistidine (3-MH) by measurement of its urinary excretion in spontaneously diabetic "BB" Wistar rats. Prior to overt diabetes, rates of excretion were appropriate to the age of the rats (1.46 +/- 0.15 mumole/day), with 34%-47% as the nonacetylated form. Accompanying diabetes there was an increase in urine urea nitrogen of two to threefold over 4-14 days, and an increase in ammonium nitrogen of sixfold. 3-MH excretion doubled by 4 days, and 81%-96% was excreted as the nonacetylated form. Subcutaneous insulin in doses sufficient to improve glycosuria and hyperglycemia was associated with normalized total 3-MH excretion (N-acetyl 3-MH plus 3-MH) but a greater proportion than normal appeared in the nonacetylated form. These results suggest that muscle protein catabolism increased with insulin deficiency and that this defect can be corrected by therapy. Both untreated and treated diabetic rats appear to have a limited capacity for acetylation of 3-MH prior to its excretion.