TY - JOUR
T1 - Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery
AU - Hansen, Jakob S
AU - Zhao, Xinjie
AU - Irmler, Martin
AU - Liu, Xinyu
AU - Hoene, Miriam
AU - Scheler, Mika
AU - Li, Yanjie
AU - Beckers, Johannes
AU - Hrabĕ de Angelis, Martin
AU - Häring, Hans-Ulrich
AU - Pedersen, Bente K
AU - Lehmann, Rainer
AU - Xu, Guowang
AU - Plomgaard, Peter
AU - Weigert, Cora
PY - 2015/8/23
Y1 - 2015/8/23
N2 - Aims/hypothesis: 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 (V⋅O2max$$ \overset{\cdot }{V}{\mathrm{O}}_{2 \max } $$). 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/interpretation: 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.
AB - Aims/hypothesis: 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 (V⋅O2max$$ \overset{\cdot }{V}{\mathrm{O}}_{2 \max } $$). 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/interpretation: 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.
KW - Amino Acids
KW - Blood Glucose
KW - Calorimetry, Indirect
KW - Carbohydrate Metabolism
KW - Diabetes Mellitus, Type 2
KW - Exercise
KW - Glucose
KW - Humans
KW - Hypoglycemic Agents
KW - Male
KW - Metformin
KW - Middle Aged
KW - Muscle, Skeletal
KW - Oxygen Consumption
KW - Sulfonylurea Compounds
U2 - 10.1007/s00125-015-3584-x
DO - 10.1007/s00125-015-3584-x
M3 - Journal article
C2 - 26067360
SN - 0012-186X
VL - 58
SP - 1845
EP - 1854
JO - Diabetologia
JF - Diabetologia
IS - 8
ER -
