title: Physiological and molecular determinants of insulin action in the baboon.
abstract: OBJECTIVE
  To quantitate insulin sensitivity in lean and obese nondiabetic baboons and examine the underlying cellular/molecular mechanisms responsible for impaired insulin action to characterize a baboon model of insulin resistance.
  
  
  METHODS
  Twenty baboons received a hyperinsulinemic-euglycemic clamp with skeletal muscle and visceral adipose tissue biopsies at baseline and at 30 and 120 min after insulin. Genes and protein expression of key molecules involved in the insulin signaling cascade (insulin receptor, insulin receptor substrate-1, p85, phosphatidylinositol 3-kinase, Akt, and AS160) were sequenced, and insulin-mediated changes were analyzed.
  
  
  RESULTS
  Overall, baboons show a wide range of insulin sensitivity (6.2 +/- 4.8 mg x kg(-1) x min(-1)), and there is a strong inverse correlation between indexes of adiposity and insulin sensitivity (r = -0.946, P < 0.001 for % body fat; r = -0.72, P < 0.001 for waist circumference). The genes and protein sequences analyzed were found to have approximately 98% identity to those of man. Insulin-mediated changes in key signaling molecules were impaired both in muscle and adipose tissue in obese insulin-resistant compared with lean insulin-sensitive baboons.
  
  
  CONCLUSIONS
  The obese baboon is a pertinent nonhuman primate model to examine the underlying cellular/molecular mechanisms responsible for insulin resistance and eventual development of type 2 diabetes.
authors.affiliation: Diabetes Division, Department of Medicine, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA.
authors.forename: Alberto O
authors.initials: AO
authors.lastname: Chavez
authors.forename: Juan C
authors.initials: JC
authors.lastname: Lopez-Alvarenga
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Tejero
authors.forename: Curtis
authors.initials: C
authors.lastname: Triplitt
authors.forename: Raul A
authors.initials: RA
authors.lastname: Bastarrachea
authors.forename: Apiradee
authors.initials: A
authors.lastname: Sriwijitkamol
authors.forename: Puntip
authors.initials: P
authors.lastname: Tantiwong
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.forename: Nicolas
authors.initials: N
authors.lastname: Musi
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
authors.forename: Franco
authors.initials: F
authors.lastname: Folli
mesh_terms: D000818:Animals; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D005260:Female; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism; D007328:Insulin / Q000097:blood / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D009765:Obesity / Q000473:pathology / Q000503:physiopathology; D010215:Papio; D013851:Thinness / Q000473:pathology / Q000503:physiopathology
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin