title: Exercise under hyperinsulinaemic conditions increases whole-body glucose disposal without affecting muscle glycogen utilisation in type 1 diabetes.
abstract: OBJECTIVE
  We examined whole-body and muscle metabolism in patients with type 1 diabetes during moderate exercise at differing circulating insulin concentrations.
  
  
  METHODS
  Eight men (mean +/- SEM age 36.4 +/- 1.5 years; diabetes duration 11.3 +/- 1.4 years; BMI 24.6 +/- 0.7 kg/m(2); HbA(1c) 7.9 +/- 0.2% and VO(2) peak 44.5 +/- 1.2 ml kg(-1) min(-1)) with type 1 diabetes were studied on two occasions at rest (2 h) and during 45 min of cycling at 60% maximum VO(2) with insulin infused at the rate of either 15 (LO study) or 50 (HI) mU m(-2) min(-1) and blood glucose clamped at 8 mmol/l. Indirect calorimetry, insulin-glucose clamps and thigh muscle biopsies were employed to measure whole-body energy and muscle metabolism.
  
  
  RESULTS
  Fat oxidation contributed 15 and 23% to total energy expenditure during exercise in the HI and LO studies, respectively. The respective carbohydrate (CHO) oxidation rates were 31.7 +/- 2.7 and 27.8 +/- 1.9 mg kg(-1) min(-1) (p < 0.05). Exogenous glucose utilisation rate during exercise was substantially greater (p < 0.001) in the HI study (18.4 +/- 2.1 mg kg(-1) min(-1)) than in the LO study (6.9 +/- 1.2 mg kg(-1) min(-1)). Muscle glycogen content fell by approximately 40% during exercise in both trials. Muscle glycogen utilisation, muscle intermediary metabolism, and phosphorylation of protein kinase B/Akt, glycogen synthase kinase 3alpha/beta and extracellular signal-regulated protein kinase 1 and 2 proteins were no different between interventions.
  
  
  CONCLUSIONS
  In patients with type 1 diabetes, exercise under peak therapeutic insulin concentrations increases exogenous glucose utilisation but does not spare muscle glycogen utilisation. A disproportionate increase in exogenous glucose utilisation relative to the increase in CHO oxidation suggests an increase in glucose flux through non-oxidative pathways.
authors.affiliation: Department of Diabetes and Endocrinology, Queen's Medical Centre, Nottingham, UK.
authors.forename: K
authors.initials: K
authors.lastname: Chokkalingam
authors.forename: K
authors.initials: K
authors.lastname: Tsintzas
authors.forename: L
authors.initials: L
authors.lastname: Norton
authors.forename: K
authors.initials: K
authors.lastname: Jewell
authors.forename: I A
authors.initials: IA
authors.lastname: Macdonald
authors.forename: P I
authors.initials: PI
authors.lastname: Mansell
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D004734:Energy Metabolism; D015444:Exercise / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology*; D010101:Oxygen Consumption
chemical_list: D001786:Blood Glucose; D007328:Insulin; D006003:Glycogen; D005947:Glucose