Physiological and molecular determinants of insulin action in the baboon.
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.
Chavez
Alberto O
AO
Diabetes Division, Department of Medicine, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA.
Lopez-Alvarenga
Juan C
JC
Tejero
M Elizabeth
ME
Triplitt
Curtis
C
Bastarrachea
Raul A
RA
Sriwijitkamol
Apiradee
A
Tantiwong
Puntip
P
Voruganti
V Saroja
VS
Musi
Nicolas
N
Comuzzie
Anthony G
AG
DeFronzo
Ralph A
RA
Folli
Franco
F
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
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin