title: Effects of type 2 diabetes and insulin on whole-body, splanchnic, and leg protein metabolism.
abstract: BACKGROUND
  Type 2 diabetes (T2D) is characterized by insulin resistance to glucose metabolism. Most studies suggest that protein metabolism is unaffected by T2D, but regional protein metabolism and response to multiple doses of insulin have not been examined.
  
  
  OBJECTIVE
  Our objective was to determine whether insulin regulation of splanchnic and leg protein metabolism are affected by T2D during hyperglycemia and graded insulin levels.
  
  
  METHODS
  We conducted a cross-sectional study at an academic medical center.
  
  
  METHODS
  T2D and non-T2D adults were matched for age (62 yr) and body mass index (30 kg/m(2)).
  
  
  METHODS
  Glucose was maintained at approximately 9 mmol/liter while insulin was infused at three progressively higher rates, achieving circulating concentrations of approximately 150, 350, and 700 pmol/liter, respectively.
  
  
  METHODS
  Protein kinetics were measured using labeled phenylalanine (Phe) and tyrosine (Tyr).
  
  
  RESULTS
  Whole-body protein breakdown and synthesis rates were higher in T2D but declined with increasing insulin in both groups. Leg Phe and Tyr appearance and disappearance and estimates of protein breakdown and synthesis, respectively, were higher in T2D but did not decline significantly with insulin, resulting in similar net balance between groups. Splanchnic response to insulin was blunted in T2D, shown by a smaller reduction in rates of disappearance and net balance of Phe and Tyr as insulin increased. Splanchnic conversion of Phe to Tyr was lower in T2D and less sensitive to insulin, whereas nonsplanchnic Phe to Tyr tended to be higher in T2D.
  
  
  CONCLUSIONS
  T2D results in higher whole-body, splanchnic, and leg protein turnover and blunts the insulin-mediated suppression of splanchnic protein anabolism under hyperglycemic, hyperinsulinemic conditions.
authors.affiliation: Mayo College of Medicine, Endocrinology Research Unit, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Short
authors.forename: Brian A
authors.initials: BA
authors.lastname: Irving
authors.forename: Ananda
authors.initials: A
authors.lastname: Basu
authors.forename: C Michael
authors.initials: CM
authors.lastname: Johnson
authors.forename: K Sreekumaran
authors.initials: KS
authors.lastname: Nair
authors.forename: Rita
authors.initials: R
authors.lastname: Basu
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D001783:Blood Flow Velocity / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007866:Leg / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000187:drug effects* / Q000378:metabolism; D013152:Splanchnic Circulation / Q000187:drug effects; D014781:Viscera / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000596:Amino Acids; D007328:Insulin; D011506:Proteins