title: Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery.
abstract: Roux-en-Y gastric bypass (RYGB) leads to increased peripheral insulin sensitivity. The aim of this study was to investigate the effect of RYGB on expression and regulation of proteins involved in regulation of peripheral glucose metabolism. Skeletal muscle and adipose tissue biopsies from glucose-tolerant and type 2 diabetic subjects at fasting and during a hyperinsulinemic-euglycemic clamp before as well as 1 wk and 3 and 12 mo after RYGB were analyzed for relevant insulin effector proteins/signaling components. Improvement in peripheral insulin sensitivity mainly occurred at 12 mo postsurgery when major weight loss was evident and occurred concomitantly with alterations in plasma adiponectin and in protein expression/signaling in peripheral tissues. In skeletal muscle, protein expression of GLUT4, phosphorylated levels of TBC1D4, as well as insulin-induced changes in phosphorylation of Akt and glycogen synthase activity were enhanced 12 mo postsurgery. In adipose tissue, protein expression of GLUT4, Akt2, TBC1D4, and acetyl-CoA carboxylase (ACC), phosphorylated levels of AMP-activated protein kinase and ACC, as well as insulin-induced changes in phosphorylation of Akt and TBC1D4, were enhanced 12 mo postsurgery. Adipose tissue from glucose-tolerant subjects was the most responsive to RYGB compared with type 2 diabetic patients, whereas changes in skeletal muscle were largely similar in these two groups. In conclusion, an improved molecular insulin-sensitive phenotype of skeletal muscle and adipose tissue appears to contribute to the improved whole body insulin action following a substantial weight loss after RYGB.
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, the August Krogh Centre, University of Copenhagen, Copenhagen, Denmark; Diabetes Research Unit, Novo Nordisk A/S, Maaloev, Denmark;
authors.forename: Peter H
authors.initials: PH
authors.lastname: Albers
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark; Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; and.
authors.forename: Kirstine N
authors.initials: KN
authors.lastname: Bojsen-Møller
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark; Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; and.
authors.forename: Carsten
authors.initials: C
authors.lastname: Dirksen
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, the August Krogh Centre, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Annette K
authors.initials: AK
authors.lastname: Serup
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, the August Krogh Centre, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Dorte E
authors.initials: DE
authors.lastname: Kristensen
authors.affiliation: Medical Research Laboratory, Department of Clinical Medicine, Health, Aarhus University, Aarhus, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.affiliation: Diabetes Research Unit, Novo Nordisk A/S, Maaloev, Denmark;
authors.forename: Trine R
authors.initials: TR
authors.lastname: Clausen
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, the August Krogh Centre, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Bente
authors.initials: B
authors.lastname: Kiens
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, the August Krogh Centre, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Erik A
authors.initials: EA
authors.lastname: Richter
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark;
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, the August Krogh Centre, University of Copenhagen, Copenhagen, Denmark; Jwojtaszewski@ifi.ku.dk.
authors.forename: Jørgen F P
authors.initials: JF
authors.lastname: Wojtaszewski
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D004734:Energy Metabolism; D005260:Female; D015390:Gastric Bypass; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D010641:Phenotype; D052097:Quadriceps Muscle / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction; D050507:Subcutaneous Fat, Abdominal / Q000201:enzymology / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D007328:Insulin
keywords: bariatric surgery; insulin sensitivity; weight loss