Insulin resistance and impaired insulin secretion in prenatally androgenized male rhesus monkeys.
Polycystic ovary syndrome (PCOS) is a familial disease. Affected males harbor some of the metabolic deficits seen in affected females. The prenatally androgenized (PA) female rhesus monkey, an animal model for PCOS, manifests glucoregulatory and reproductive abnormalities similar to those seen in PCOS women. The purpose of this study was to determine whether exposure of fetal male rhesus monkeys to testosterone excess would induce glucoregulatory and reproductive deficits. Seven adult PA males and seven matched controls underwent somatometric measurements, sex steroid analysis, and a frequently sampled i.v. glucose tolerance test. Body measurements were similar in the two groups, although arm circumference was greater in control compared with PA males (P < 0.01). There were no differences in neonatal weight or serum levels of sex steroids between the two male groups. Measures of insulin sensitivity and pancreatic beta-cell compensation (disposition index) were clearly diminished in PA compared with control males [insulin sensitivity: PA, mean 0.8 (95% confidence interval, 0.11, 5.82); controls, 3.06 (1.51, 6.19) x 10(-4)/min/microU/ml; P < 0.05; disposition index: PA, 226.38 (69.54, 383.22); controls, 509.21/min (306.52, 711.89); P < 0.02]. PA males do not exhibit elevated androgens during adulthood, suggesting that insulin resistance and impaired pancreatic beta-cell function may result from fetal reprogramming of key metabolic tissues.
Bruns
Cristin M
CM
Department of Medicine, University of Wisconsin, Madison, Wisconsin 53792, USA. cb2@medicine.wisc.edu
Baum
Scott T
ST
Colman
Ricki J
RJ
Eisner
Joel R
JR
Kemnitz
Joseph W
JW
Weindruch
Richard
R
Abbott
David H
DH
D000818:Animals; D019540:Area Under Curve; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013739:Testosterone / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology
D007004:Hypoglycemic Agents; D007328:Insulin; D013739:Testosterone; D014044:Tolbutamide; D005947:Glucose