Effects of Insulin and Amino Acids on Leg Protein Turnover in IDDM Patients

Abstract

To determine whether the responses of muscle protein metabolism to insulin and amino acids in patients with insulin-dependent diabetes mellitus (IDDM) were different from those in nondiabetic subjects, leg tissue kinetics of [15N]phenylalanine and [1-13C]leucine and its metabolites were measured in eight insulin-withdrawn IDDM patients and eight nondiabetic subjects during basal insulinemia and during infusion of insulin (0.29 nmol.min-1.m-2). The diabetic patients were studied in the absence of amino acids, and both groups were studied during infusion of a mixed-amino acid solution (AA). In the diabetic patients, insulin alone and combined with additional AA reduced leg tissue phenylalanine release by 42 and 41%, respectively (both P less than 0.05), but uptake was unchanged. Leg tissue leucine oxidation was unchanged by insulin alone but was increased (P = 0.012) fourfold during insulin infusion with additional AA. In the nondiabetic subjects, insulin with AA infusion increased leg tissue phenylalanine uptake (45.7 +/- 7.5 to 73.1 +/- 7.3 nmol.min-1.100 g-1, P less than 0.01). Insulin-stimulated glucose uptake in the diabetic patients (1.60 +/- 0.28 mumol.min-1.100 g-1, P = 0.04). These results suggest that, in IDDM patients, 1) infusion of insulin fails to stimulate muscle protein synthesis even when combined with a substantially increased provision of AA, and 2) compared with nondiabetic subjects, muscle protein synthesis as well as glucose uptake exhibit blunted responses to insulin.

The potential role of glutamate in the current diabetes epidemic

“…It is noteworthy that in these women, protein turnover was normalized by insulin treatment, but fasting and postprandial glutamate levels remained elevated despite the satisfactory glycemic control. There is clear evidence of altered protein metabolism also in T1D [176][177][178][179][180]. In T1D, insulin deficiency increases protein breakdown and the associated hyperglucagonemia accelerates protein catabolism [181].…”

“…Acta Diabetol (2012) 49:[167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182][183] …”

Role of hyperglucagonemia in catabolism associated with type 1 diabetes: effects on leucine metabolism and the resting metabolic rate.

“…Sir William Osler, almost a 100 years ago, described the disease in terms of "progressive emaciation," involving massive urinary losses of both glucose and urea in diabetic patients (2). Insulin treatment not only improves control of glucose levels but also has a profound effect on protein metabolism, correcting increased urinary losses of nitrogen and increasing whole-body protein accretion, as indicated by whole-body potassium measurements (3)(4)(5)(6). It remains to be clearly defined whether insulin d e fic i e n c y, per se, is the cause of the catabolic state that occurs in poorly controlled type 1 diabetes.…”

Mechanism of insulin's anabolic effect on muscle: measurements of muscle protein synthesis and breakdown using aminoacyl-tRNA and other surrogate measures

“…In vitro evidence indicates that insulin decreases skeletal muscle protein breakdown (2,22,24,31) and increases muscle protein synthesis (2,22,23,33,35). In humans, systemic insulin administration inhibits muscle protein breakdown in patients with T1DM (6,8,30,34) and in healthy subjects (13,29) but not confirmed by all studies (38). Systemic insulin administration causes hypoaminoacidemia, which may potentially affect muscle protein kinetics, since it has been shown that amino acids (AA) play a key regulatory role on insulin effect on protein synthesis and breakdown (16,21,27).…”