title: AMPK in the small intestine in normal and pathophysiological conditions.
abstract: The role of AMPK in regulating energy storage and depletion remains unexplored in the intestine. This study will to define its status, composition, regulation and lipid function, as well as to examine the impact of insulin resistance and type 2 diabetes on intestinal AMPK activation, insulin sensitivity, and lipid metabolism. Caco-2/15 cells and Psammomys obesus (P. obesus) animal models were experimented. We showed the predominance of AMPKα1 and the prevalence of α1/β2/γ1 heterotrimer in Caco-2/15 cells. The activation of AMPK by 5-aminoimidazole-4-carboxamide ribonucleoside and metformin resulted in increased phospho(p)-ACC. However, the down-regulation of p-AMPK by compound C and high glucose lowered p-ACC without affecting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Administration of metformin to P. obesus with insulin resistance and type 2 diabetes led to 1) an up-regulation of intestinal AMPK signaling pathway typified by ascending p-AMPKα(-Thr172); 2) a reduction in ACC activity; 3) an elevation of carnitine palmitoyltransferase 1; 4) a trend of increase in insulin sensitivity portrayed by augmentation of p-Akt and phospho-glycogen synthetase kinase 3β; 5) a reduced phosphorylation of p38-MAPK and ERK1/2; and 6) a decrease in diabetic dyslipidemia following lowering of intracellular events that govern lipoprotein assembly. These data suggest that AMPK fulfills key functions in metabolic processes in the small intestine.
authors.affiliation: Research Center (E.H., E.G., A.B.O., M.E.C., A.S., S.S., E.L.), Sainte-Justine MUHC, Montreal, Quebec, Canada, H3T 1C5; Department of Nutrition (E.H., E.G., S.S., E.L.) and Department of Biochemistry (M.E.C.), Université de Montréal, Montreal, Quebec, Canada, H3T 1C5; Diabetes Unit (E.Z.), Division of Internal Medicine, Hadassah Ein Kerem Hospital, 120 Jerusalem, Israel-91; Canadian Institutes for Health Research Team on the Digestive Epithelium (J.F.B., E.L.), Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada, J1H 5N4; and CRNH Rhône-Alpes (E.H., M.L.), Université Lyon 1, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1060, CENS, Centre Hospitalier Lyon-Sud, F-69310 Pierre Bénite, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Harmel
authors.forename: Emilie
authors.initials: E
authors.lastname: Grenier
authors.forename: Ali
authors.initials: A
authors.lastname: Bendjoudi Ouadda
authors.forename: Mounib
authors.initials: M
authors.lastname: El Chebly
authors.forename: Ehud
authors.initials: E
authors.lastname: Ziv
authors.forename: Jean François
authors.initials: JF
authors.lastname: Beaulieu
authors.forename: Alain
authors.initials: A
authors.lastname: Sané
authors.forename: Schohraya
authors.initials: S
authors.lastname: Spahis
authors.forename: Martine
authors.initials: M
authors.lastname: Laville
authors.forename: Emile
authors.initials: E
authors.lastname: Levy
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D018938:Caco-2 Cells; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D019281:Dimerization; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005849:Gerbillinae; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007421:Intestine, Small / Q000201:enzymology*; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D020935:MAP Kinase Signaling System; D008297:Male; D008687:Metformin / Q000737:chemistry; D008861:Microsomes / Q000378:metabolism; D009924:Organ Culture Techniques; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D007328:Insulin; D008687:Metformin; D002334:Carnitine O-Palmitoyltransferase; D000071679:Glycogen Synthase Kinase 3 beta; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; D055372:AMP-Activated Protein Kinases