title: Endurance training inhibits insulin clearance and IDE expression in Swiss mice.
abstract: BACKGROUND
  Endurance training improves peripheral insulin sensitivity in the liver and the skeletal muscle, but the mechanism for this effect is poorly understood. Recently, it was proposed that insulin clearance plays a major role in both glucose homeostasis and insulin sensitivity. Therefore, our goal was to determine the mechanism by which endurance training improves insulin sensitivity and how it regulates insulin clearance in mice.
  
  
  METHODS
  Mice were treadmill-trained for 4 weeks at 70-80% of maximal oxygen consumption (VO2 max) for 60 min, 5 days a week. The glucose tolerance and the insulin resistance were determined using an IPGTT and an IPITT, respectively, and the insulin decay rate was calculated from the insulin clearance. Protein expression and phosphorylation in the liver and the skeletal muscle were ascertained by Western blot.
  
  
  RESULTS
  Trained mice exhibited an increased VO2 max, time to exhaustion, glucose tolerance and insulin sensitivity. They had smaller fat pads and lower plasma concentrations of insulin and glucose. Endurance training inhibited insulin clearance and reduced expression of IDE in the liver, while also inhibiting insulin secretion by pancreatic islets. There was increased phosphorylation of both the canonical (IR-AKT) and the non-canonical (CaMKII-AMPK-ACC) insulin pathways in the liver of trained mice, whereas only the CaMKII-AMPK pathway was increased in the skeletal muscle.
  
  
  CONCLUSIONS
  Endurance training improved glucose homeostasis not only by increasing peripheral insulin sensitivity but also by decreasing insulin clearance and reducing IDE expression in the liver.
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
authors.forename: José M
authors.initials: JM
authors.lastname: Costa-Júnior
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Ferreira
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
authors.forename: André O
authors.initials: AO
authors.lastname: Protzek
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
authors.forename: Gustavo J
authors.initials: GJ
authors.lastname: Santos
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Cappelli
authors.affiliation: Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo (USP), Ribeirão Preto, SP, Brazil.
authors.forename: Leonardo R
authors.initials: LR
authors.lastname: Silveira
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
authors.forename: Cláudio
authors.initials: C
authors.lastname: Zoppi
authors.affiliation: Department of Biosciences, Federal University of Sao Paulo (Unifesp), Santos, SP, CEP 11060-001, Brazil.
authors.forename: Camila A M
authors.initials: CA
authors.lastname: de Oliveira
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Boschero
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
authors.forename: Everardo M
authors.initials: EM
authors.lastname: Carneiro
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Rezende
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D007333:Insulin Resistance; D007339:Insulysin / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D010101:Oxygen Consumption; D005082:Physical Exertion; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011972:Receptor, Insulin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D055372:AMP-Activated Protein Kinases; D007339:Insulysin
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