title: Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery.
abstract: OBJECTIVE
  The therapeutic benefit of physical activity to prevent and treat type 2 diabetes is commonly accepted. However, the impact of the disease on the acute metabolic response is less clear. To this end, we investigated the effect of type 2 diabetes on exercise-induced plasma metabolite changes and the muscular transcriptional response using a complementary metabolomics/transcriptomics approach.
  
  
  METHODS
  We analysed 139 plasma metabolites and hormones at nine time points, and whole genome expression in skeletal muscle at three time points, during a 60 min bicycle ergometer exercise and a 180 min recovery phase in type 2 diabetic patients and healthy controls matched for age, percentage body fat and maximal oxygen consumption (VO2).
  
  
  RESULTS
  Pathway analysis of differentially regulated genes upon exercise revealed upregulation of regulators of GLUT4 (SLC2A4RG, FLOT1, EXOC7, RAB13, RABGAP1 and CBLB), glycolysis (HK2, PFKFB1, PFKFB3, PFKM, FBP2 and LDHA) and insulin signal mediators in diabetic participants compared with controls. Notably, diabetic participants had normalised rates of lactate and insulin levels, and of glucose appearance and disappearance, after exercise. They also showed an exercise-induced compensatory regulation of genes involved in biosynthesis and metabolism of amino acids (PSPH, GATM, NOS1 and GLDC), which responded to differences in the amino acid profile (consistently lower plasma levels of glycine, cysteine and arginine). Markers of fat oxidation (acylcarnitines) and lipolysis (glycerol) did not indicate impaired metabolic flexibility during exercise in diabetic participants.
  
  
  CONCLUSIONS
  Type 2 diabetic individuals showed specific exercise-regulated gene expression. These data provide novel insight into potential mechanisms to ameliorate the disturbed glucose and amino acid metabolism associated with type 2 diabetes.
authors.affiliation: Centre of Inflammation and Metabolism, Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Jakob S
authors.initials: JS
authors.lastname: Hansen
authors.forename: Xinjie
authors.initials: X
authors.lastname: Zhao
authors.forename: Martin
authors.initials: M
authors.lastname: Irmler
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.forename: Miriam
authors.initials: M
authors.lastname: Hoene
authors.forename: Mika
authors.initials: M
authors.lastname: Scheler
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Li
authors.forename: Johannes
authors.initials: J
authors.lastname: Beckers
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabĕ de Angelis
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.forename: Bente K
authors.initials: BK
authors.lastname: Pedersen
authors.forename: Rainer
authors.initials: R
authors.lastname: Lehmann
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
authors.forename: Peter
authors.initials: P
authors.lastname: Plomgaard
authors.forename: Cora
authors.initials: C
authors.lastname: Weigert
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect; D050260:Carbohydrate Metabolism / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015444:Exercise / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D010101:Oxygen Consumption; D013453:Sulfonylurea Compounds / Q000627:therapeutic use
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C057619:glimepiride; D008687:Metformin; D005947:Glucose