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Métabolisme hépatocytaire et insulinorésistance : Effets d'un régime enrichi en graisses et d'un nouvel antidiabétique « E008 »

Abstract : With a steadily increasing prevalence, type II diabetes is becoming a major public health issue. This pathology is characterized by an increase of the hepatic glucose production, reflecting a raise of gluconeogenesis, which evolves into chronic hyperglycemia. Liver is thus a privileged target to fight against imbalances of glucose metabolism. A new drug derived from the Metformin and devoid of side effects, the E008, was synthesized by Merck-Santé to normalize blood glucose levels in diabetic patients. The dual objective of our work consisted in (i) studying liver metabolic fluxes in a nutritional rat model which exhibits a metabolic syndrome, and (ii) analysing the effects of this new compound while elucidating its mechanisms of action. Animals fed a high-fat diet have an increased gluconeogenesis, associated with disturbances of the mitochondrial function: increase of ROS production, inhibition of oxygen consumption and changes in redox potential. A common denominator in these events could be a mutual alteration of the composition of membrane lipids and quinones. On rats fed with a high-fat diet, E008 treatment decreases the hepatic glucose output by modifying metabolic control. Furthermore, it induces a subtle inhibition of cellular respiration while acting, at the same time, on the respiratory chain activity and phosphorylating system. (Inhibition of complex I and ANT reduced expression). Its action is also related to an activation of AMP-activated protein kinase (AMPK), by modification of adenine nucleotides ratios.
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https://tel.archives-ouvertes.fr/tel-00444169
Contributor : Guillaume Vial <>
Submitted on : Wednesday, January 6, 2010 - 8:42:59 AM
Last modification on : Thursday, November 19, 2020 - 3:52:36 PM
Long-term archiving on: : Thursday, June 17, 2010 - 8:08:59 PM

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Guillaume Vial. Métabolisme hépatocytaire et insulinorésistance : Effets d'un régime enrichi en graisses et d'un nouvel antidiabétique « E008 ». Sciences du Vivant [q-bio]. Université Joseph-Fourier - Grenoble I, 2009. Français. ⟨tel-00444169⟩

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