REGULATION OF POSTPRANDIAL WHOLE-BODY PROTEOLYSIS IN INSULIN-DEPRIVED IDDM

Suppression of tissue proteolysis is an important mechanism of postprandial protein anabolism, and it may be mediated by insulin, hyperaminoacidemia, or both. To evaluate whether insulin is essential in the regulation of this process, we have investigated the effect of mixed-meal ingestion on whole-body protein breakdown in insulin-deprived insulin-dependent diabetes mellitus (IDDM) patients and normal control subjects. Endogenous phenylalanine and leucine rate of appearance (R(a)) from proteolysis were measured at steady-state conditions using a multiple stable isotope technique before and after the constant administration of a synthetic mixed meal. In the postabsorptive state, the IDDM patients exhibited accelerated intracellular leucine R(a) (IDDM, 2.64 +/- 0.19 mu mol.min(-1).kg(-1); control, 2.02 +/- 0.03 mu mol.min(-1). kg(-1); P < 0.05) and plasma phenylalanine R(a) (IDDM, 0.73 +/- 0.03 mu mol.min(-1).kg(-1); control, 0.61 +/- 0.04 mu mol. min(-1).kg(-1); P < 0.05). During meal ingestion, endogenous phenylalanine and leucine R(a) values were suppressed in both the insulin-deficient IDDM (P < 0.05) and control subjects (P < 0.05). Although postmeal endogenous leucine and phenylalanine R(a) values remained greater (P < 0.05) in IDDM, the Delta changes from the basal endogenous leucine R(a) (IDDM, -0.56 +/- 0.11 mu mol. min(-1).kg(-1); control, -0.56 +/- 0.09 mu mol.min(-1).kg(-1)) and phenylalanine R(a) (IDDM, -0.13 +/- 0.01 mu mol . min(-1).kg(-1); control, -0.14 +/- 0.02 mu mol.min(-1).kg(-1)) were similar in both groups. In the IDDM patients, the postmeal increases from the basal leucine concentration were onefold greater (P < 0.05) than in the control subjects. In conclusion, in IDDM patients, whole-body proteolysis was suppressed during meal ingestion despite insulin withdrawal, which was possibly mediated by excessive hyperaminoacidemia.