Skeletal muscle protein anabolic response to increased energy and insulin is preserved in poorly controlled type 2 diabetes

Abstract

Type 2 diabetes (T2DM) subjects failing diet treatment are characterized by hyperinsulinemia and insulin resistance leading to fasting and postprandial hyperglycemia and hyperlipidemia. Energy is essential for allowing the process of protein synthesis to proceed. Additionally, insulin can stimulate protein synthesis in human muscle. The aims of this study were to determine if poorly controlled T2DM affects postabsorptive muscle protein anabolism, and if the muscle anabolic response to hyperinsulinemia with high energy availability is maintained. Control (n = 6) and T2DM subjects (n = 6) were studied in the postabsorptive state and during an isoenergetic high nutritional energy clamp (relative to postabsorptive state). Muscle protein synthesis and breakdown (nmol . min(-1) . 100 g leg muscle(-1)) were assessed using stable isotope methodology, femoral arterio-venous sampling, muscle biopsies, and a three-pool model to calculate protein turnover. Postabsorptive phenylalanine net balance and whole body rate of appearance (Ra) were not different between groups; however, basal muscle protein breakdown was higher in T2DM (94 +/- 9) than in controls (58 +/- 12) (P < 0.05) and muscle protein synthesis tended (P = 0.07) to be elevated in T2DM (66 +/- 14) compared with controls (39 +/- 6). During the clamp, net balance increased, whole body Ra and muscle protein breakdown decreased (P < 0.05), and muscle protein synthesis tended to decrease (P = 0.08) to a similar extent in both groups. We conclude that postabsorptive muscle protein turnover is elevated in poorly controlled T2DM, however, there is no excessive loss of muscle protein because net balance is not different from controls. Moreover, the anabolic response to increased insulin and energy availability is maintained in T2DM.

Figures

FIGURE 1

Study design consisting of a basal postabsorptive period and a high energy-hyperinsulinemic clamp period. ICG, indocyanine green.

FIGURE 2

Shown are 2- and 3-pool compartment models of leg phenylalanine (phe) kinetics. Free phe pools in femoral artery (A), femoral vein (V) and muscle (M) are connected by arrows indicating unidirectional phe flow in each compartment. With both models, phe enters the leg via femoral artery (Fin) and leaves the leg via femoral vein (Fout). For the 2-pool model, Rd is the rate of phe disappearance (estimate of protein synthesis) and Ra is the rate of phe appearance from breakdown. For the 3-pool model, FV,A is direct phenylalanine flow from artery to vein without entering intracellular fluid. FM,A and FV,M are inward and outward transport from artery to muscle and from muscle to vein, respectively. FM,0, intracellular phenylalanine appearance (breakdown). F0,M is intracellular phenylalanine disappearance (protein synthesis). F0,M / (FM,0+FM,A) is protein synthesis efficiency.

FIGURE 3

Muscle protein breakdown in controls and T2DM subjects under basal postabsorptive and clamp conditions. Values are means ± SEM, n = 6. * Different from basal, P < 0.05. # Different from controls, P < 0.05.