title: Voluntary physical activity and leucine correct impairments in muscle protein synthesis in partially pancreatectomised rats.
abstract: OBJECTIVE
  Poorly controlled type 1 diabetes mellitus can cause reduced skeletal muscle mass and weakness during adolescence, which may affect long-term management of the disease. The aim of this study was to determine whether regular voluntary physical activity and leucine feeding restore rates of protein synthesis and deficits in skeletal muscle mass in a young, hypoinsulinaemic/hyperglycaemic rat model of diabetes.
  
  
  METHODS
  Four-week-old male Sprague-Dawley rats were partially pancreatectomised (Px) to induce hypoinsulinaemia/hyperglycaemia and housed with/without access to running wheels for 3 weeks (n = 12-14/group). Sham surgery rats (shams) served as sedentary controls (n = 18). Protein synthesis and markers of protein anabolism were assessed in the fasted state and following leucine gavage. Fibre type and cross-sectional areas of the gastrocnemius muscle were measured using a metachromatic ATPase stain.
  
  
  RESULTS
  Compared with sedentary behaviour, regular activity lowered fasting glycaemia and reduced fed hyperglycaemia in Px rats. Active-Px rats, which ran 2.2  ±  0.71 km/night, displayed greater muscle mass and fibre areas similar to shams, while sedentary-Px rats displayed a 20-30% loss in muscle fibre areas. Muscle protein synthesis (basal and in response to leucine gavage) was impaired in sedentary-Px (by ~65%), but not in active-Px rats, when compared with shams. Following leucine gavage, the phosphorylation status of eIF4E binding protein 1 (4E-BP1) and ribosomal S6 kinase 1 (S6K1), markers of mammalian target of rapamycin complex 1 (mTORC1) signalling, increased in shams (by two- and ninefold, respectively) and in active-Px (1.5- and fourfold, respectively) rats, but not in sedentary-Px rats.
  
  
  CONCLUSIONS
  Moderate physical activity in young Px rats normalises impairments in skeletal muscle growth and protein synthesis. These findings illustrate the critical compensatory role that modest physical activity and targeted nutrition can have on skeletal muscle growth during periods of hypoinsulinaemia in adolescent diabetes.
authors: School of Kinesiology and Health Science, York University, 4700 Keele Street, Toronto, ON, Canada.
authors: A S
authors: AS
authors: Serino
authors: O A
authors: OA
authors: Adegoke
authors: S
authors: S
authors: Zargar
authors: C S
authors: CS
authors: Gordon
authors: A A
authors: AA
authors: Szigiato
authors: T J
authors: TJ
authors: Hawke
authors: M C
authors: MC
authors: Riddell
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007930:Leucine / Q000008:administration & dosage*; D008297:Male; D009043:Motor Activity; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000187:drug effects; D018482:Muscle, Skeletal / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D057185:Sedentary Behavior
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; D019893:Ribosomal Protein S6 Kinases; C526901:Rps6kb1 protein, rat; D007930:Leucine