Insulin Resistance

This book has been made possible by the contributions of leading scientists and clinicians from upcoming and interdisciplinary fields of research concerning the molecular and clinical features of insulin resistance. Multiple metabolic disturbances associated with Insulin Resistance include inflammatory cytokines, adipokines, endothelial dysfunction, tissue-specific defects in insulin action and signaling, oxidative stress, ectopic lipid deposition, and disordered neuroregulation. This book aims to encourage scientists and physicians - working separately on various aspects of Insulin resistance and metabolic syndrome for early detection of the first signs indicating the onset of a metabolic misbalance in order to prevent the consecutive cascades which lead to metabolic syndrome, resulting in the so-called diseases of modern civilization - cancer, diabetes and hypertension

13C metabolic flux analysis shows that resistin impairs the metabolic response to insulin in L6E9 myotubes

Background: It has been suggested that the adipokine resistin links obesity and insulin resistance, although how resistin acts on muscle metabolism is controversial. We aimed to quantitatively analyse the effects of resistin on the glucose metabolic flux profile and on insulin response in L6E9 myotubes at the metabolic level using a tracer-based metabolomic approach and our in-house developed software, Isodyn.Results: Resistin significantly increased glucose uptake and glycolysis, altering pyruvate utilisation by the cell. In the presence of resistin, insulin only slightly increased glucose uptake and glycolysis, and did not alter the flux profile around pyruvate induced by resistin. Resistin prevented the increase in gene expression in pyruvate dehydrogenase-E1 and the sharp decrease in gene expression in cytosolic phosphoenolpyruvate carboxykinase-1 induced by insulin.Conclusions: These data suggest that resistin impairs the metabolic activation of insulin. This impairment cannot be explained by the activity of a single enzyme, but instead due to reorganisation of the whole metabolic flux distribution.Peer reviewed: YesNRC publication: Ye