title: Slow-twitch fiber proportion in skeletal muscle correlates with insulin responsiveness.
abstract: BACKGROUND
  The metabolic syndrome, characterized by central obesity with dyslipidemia, hypertension, and hyperglycemia, identifies people at high risk for type 2 diabetes.
  
  
  OBJECTIVE
  Our objective was to determine how the insulin resistance of the metabolic syndrome is related to muscle fiber composition.
  
  
  METHODS
  Thirty-nine sedentary men and women (including 22 with the metabolic syndrome) had insulin responsiveness quantified using euglycemic clamps and underwent biopsies of the vastus lateralis muscle. Expression of insulin receptors, insulin receptor substrate-1, glucose transporter 4, and ATP synthase were quantified with immunoblots and immunohistochemistry.
  
  
  METHODS
  Participants were nondiabetic, metabolic syndrome volunteers and sedentary control subjects studied at an outpatient clinic.
  
  
  METHODS
  Insulin responsiveness during an insulin clamp and the fiber composition of a muscle biopsy specimen were evaluated.
  
  
  RESULTS
  There were fewer type I fibers and more mixed (type IIa) fibers in metabolic syndrome subjects. Insulin responsiveness and maximal oxygen uptake correlated with the proportion of type I fibers. Insulin receptor, insulin receptor substrate-1, and glucose transporter 4 expression were not different in whole muscle but all were significantly less in the type I fibers of metabolic syndrome subjects when adjusted for fiber proportion and fiber size. Fat oxidation and muscle mitochondrial expression were not different in the metabolic syndrome subjects.
  
  
  CONCLUSIONS
  Lower proportion of type I fibers in metabolic syndrome muscle correlated with the severity of insulin resistance. Even though whole muscle content was normal, key elements of insulin action were consistently less in type I muscle fibers, suggesting their distribution was important in mediating insulin effects.
authors.affiliation: Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, P.O. Box 70622, Johnson City, Tennessee 37614-0622, USA. stuartc@etsu.edu
authors.forename: Charles A
authors.initials: CA
authors.lastname: Stuart
authors.forename: Melanie P
authors.initials: MP
authors.lastname: McCurry
authors.forename: Anna
authors.initials: A
authors.lastname: Marino
authors.forename: Mark A
authors.initials: MA
authors.lastname: South
authors.forename: Mary E A
authors.initials: ME
authors.lastname: Howell
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Layne
authors.forename: Michael W
authors.initials: MW
authors.lastname: Ramsey
authors.forename: Michael H
authors.initials: MH
authors.lastname: Stone
mesh_terms: D025181:ATP Synthetase Complexes / Q000378:metabolism; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000209:etiology; D005260:Female; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018657:Muscle Fibers, Slow-Twitch / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D009765:Obesity / Q000150:complications; D052097:Quadriceps Muscle / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D011972:Receptor, Insulin / Q000378:metabolism; D012306:Risk; D057185:Sedentary Behavior; D013714:Tennessee / Q000453:epidemiology
chemical_list: D015703:Antigens, CD; D051275:Glucose Transporter Type 4; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C495692:SLC2A4 protein, human; C435941:INSR protein, human; D011972:Receptor, Insulin; D025181:ATP Synthetase Complexes