B-13O Free Communication/Poster Skeletal Muscle Metabolism
The creatine (Cr)/phosphocreatine (PCr) system is essential for buffering and transport of high-energy phosphorus compounds especially in cells with high energy demands(1). Creatine depleted animals have enhanced glucose tolerance and improved insulin sensitivity(1). Glucose metabolism has never been studied in human Cr depletion. Gyrate atrophy (GA) is a rare inborn error of metabolism. Patients with GA have 50% PCr depletion in skeletal muscle, which provides a model of human Cr depletion in vivo.
The purpose of this study was to investigate whether insulin sensitivity is increased in Cr depletion in man.
We studied whole-body insulin sensitivity in 4 male patients (aged 33,41,47,49 years) with genetically verified GA and normal BMI (mean ±SD 21.3 ±2.2 kg/m2) using euglycemic insulin clamp technique(2). Plasma insulin was kept high by a primed continuos insulin infusion (1mU*kg-1*min-1) and normoglycemia (gluc 5mmol/l) was maintained by an infusion of 20% glucose. The rate of glucose infusion was regulated based on arterial plasma glucose every 5 minutes. Insulin sensitivity expressed as M-value (umol/kg*min) was calculated as described by DeFronzo(2). Values were compared to M-values from 31 healthy males (mean age 30.4 ±6 years; range 23 to 47 years) with normal BMI (23.2 ±1.9 kg/m2), previously studied at the same institute.
M-values of the patients with GA were 26, 25, 34 and 29. Mean M-value of the controls was 32 ±10 ranging between 14 and 45. Thus, the values from patients with GA were not increased.
In contrary to animal experiments, in this study whole-body insulin sensitivity is not increased in human Cr depletion. In fact, the M-values seem to be low. This may be explained by the lower grade of Cr depletion (50%) in this study compared to animal models (90%).
1. Wyss M, Kaddurah-Daouk R. Physiol Rev 2000 2. DeFronzo RA et al. Am J Physiol 1979