Glycogen synthesis in human gastrocnemius muscle is not representative of whole-body muscle glycogen synthesis.
ABSTRACT The introduction of 13C magnetic resonance spectroscopy (MRS) has enabled noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based on measurements by the MRS technique assume that glucose metabolism in gastrocnemius muscle is representative for all skeletal muscles and thus can be extrapolated to whole-body muscle glucose metabolism. An alternative method to assess whole-body muscle glycogen synthesis is the use of [3-(3)H]glucose. In the present study, we compared this method to the MRS technique, which is a well-validated technique for measuring muscle glycogen synthesis. Muscle glycogen synthesis was measured in the gastrocnemius muscle of six lean healthy subjects by MRS and by the isotope method during a hyperinsulinemic-euglycemic clamp. Mean muscle glycogen synthesis as measured by the isotope method was 115 +/- 26 micromol x kg(-1) muscle x min(-1) vs. 178 +/- 72 micromol x kg(-1) muscle x min(-1) (P = 0.03) measured by MRS. Glycogen synthesis rates measured by MRS exceeded 100% of glucose uptake in three of the six subjects. We conclude that glycogen synthesis rates measured in gastrocnemius muscle cannot be extrapolated to whole-body muscle glycogen synthesis.
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ABSTRACT: The objective of this study was to investigate the relationship between plasma and brain glucose levels during euglycemia and hypoglycemia in healthy subjects and patients with type 1 diabetes mellitus (T1DM). Hyperinsulinemic euglycemic (5 mmol/L) and hypoglycemic (3 mmol/L) [1-(13)C]glucose clamps were performed in eight healthy subjects and nine patients with uncomplicated T1DM (HbA(1c) 7.7 ± 1.4%). Brain glucose levels were measured by (13)C magnetic resonance spectroscopy. Linear regression analysis was used to fit the relationship between plasma and brain glucose levels and calculate reversible Michaelis-Menten (MM) kinetic parameters. Brain glucose values during euglycemia (1.1 ± 0.4 μmol/g vs. 1.1 ± 0.3 μmol/g; P = 0.95) and hypoglycemia (0.5 ± 0.2 μmol/g vs. 0.6 ± 0.3 μmol/g; P = 0.52) were comparable between healthy subjects and T1DM patients. MM kinetic parameters of combined data were calculated to be maximum transport rate/cerebral metabolic rate of glucose (T(max)/CMR(glc)) = 2.25 ± 0.32 and substrate concentration at half maximal transport (K(t)) = 1.53 ± 0.88 mmol/L, which is in line with previously published data obtained under hyperglycemic conditions. In conclusion, the linear MM relationship between plasma and brain glucose can be extended to low plasma glucose levels. We found no evidence that the plasma to brain glucose relationship or the kinetics describing glucose transport over the blood-brain barrier differ between healthy subjects and patients with uncomplicated, reasonably well-controlled T1DM.Diabetes 06/2012; 61(8):1974-7. · 7.90 Impact Factor
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ABSTRACT: The suppression of lipolysis is one of the key metabolic responses of the adipose tissue during hyperinsulinemia. The failure to respond and resulting increase in plasma fatty acids could contribute to the development of insulin resistance and perturbations in the fuel homeostasis in the whole body. In this study, a mechanistic, computational model of adipose tissue metabolism in vivo has been enhanced to simulate the physiological responses during hyperinsulinemic-euglycemic clamp experiment in humans. The model incorporates metabolic intermediates and pathways that are important in the fed state. In addition, it takes into account the heterogeneity of triose phosphate pools (glycolytic vs. glyceroneogenic), within the adipose tissue. The model can simulate not only steady-state responses at different insulin levels, but also concentration dynamics of major metabolites in the adipose tissue venous blood in accord with the in vivo data. Simulations indicate that (1) regulation of lipoprotein lipase (LPL) reaction is important when the intracellular lipolysis is suppressed by insulin; (2) intracellular diglyceride levels can affect the regulatory mechanisms; and (3) glyceroneogenesis is the dominant pathway for glycerol-3-phosphate synthesis even in the presence of increased glucose uptake by the adipose tissue. Reduced redox and increased phosphorylation states provide a favorable milieu for glyceroneogenesis in response to insulin. A parameter sensitivity analysis predicts that insulin-stimulated glucose uptake would be more severely affected by impairment of GLUT4 translocation and glycolysis than by impairment of glycogen synthesis and pyruvate oxidation. Finally, simulations predict metabolic responses to altered expression of phosphoenolpyruvate carboxykinase (PEP-CK). Specifically, the increase in the rate of re-esterification of fatty acids observed experimentally with the overexpression of PEPCK in the adipose tissue would be accompanied by the up-regulation of acyl Co-A synthase.Cellular and Molecular Bioengineering 06/2011; 4(2):281-301. · 1.44 Impact Factor
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ABSTRACT: Patients with type 1 diabetes mellitus (T1DM) experience, on average, 2 to 3 hypoglycemic episodes per week. This study investigated the effect of hypoglycemia on cerebral glucose metabolism in patients with uncomplicated T1DM. For this purpose, hyperinsulinemic euglycemic and hypoglycemic glucose clamps were performed on separate days, using [1-13C]glucose infusion to increase plasma 13C enrichment. In vivo brain 13C magnetic resonance spectroscopy was used to measure the time course of 13C label incorporation into different metabolites and to calculate the tricarboxylic acid cycle flux (VTCA) by a one-compartment metabolic model. We found that cerebral glucose metabolism, as reflected by the VTCA, was not significantly different comparing euglycemic and hypoglycemic conditions in patients with T1DM. However, the VTCA was inversely related to the HbA1C and was, under hypoglycemic conditions, approximately 45% higher than that in a previously investigated group of healthy subjects. These data suggest that the brains of patients with T1DM are better able to endure moderate hypoglycemia than those of subjects without diabetes.The Journal of clinical investigation 01/2013; · 15.39 Impact Factor