INSULIN ACTION IN THE POLYCYSTIC OVARY SYNDROME

  • Verderame, Michael (PI)
  • Dunaif, Andrea (PI)
  • Dunaif, Andrea (PI)
  • Dunaif, Andrea (PI)
  • Dunaif, Andrea (PI)
  • Dunaif, Andrea (PI)

Project: Research project

Project Details

Description

The Overall Specific Aims of this research are to determine the
mechanisms and pathogenesis of insulin resistance in the polycystic
ovary syndrome (PCO). This research will provide insight into the
cause(s) of PCO and of non-insulin dependent diabetes mellitus
(NlDDM). PCO, a hyperandrogenic disorder of unknown etiology, is
one of the most common endocrine diseases of women of reproductive
age. Women with PCO are markedly insulin resistant, independent
of obesity. But PCO and obesity have a synergistic deleterious
effect on glucose tolerance such that 20% of obese PCO women have
impaired glucose tolerance or frank NIDDM. Our preliminary
epidemiologic, family, and fibroblast insulin binding studies
strongly suggest that there is a genetic component to the insulin
resistance of PCO. Further, there is a strikingly increased
prevalence of NIDDM in families of women with PCO consistent with
a causal and/or genetic association of these disorders. The
Specific Aims of this proposal are: 1) To Characterize in Detail
the Mechanisms of Insulin Resistance In Vivo in PCO. This will be
accomplished by defining the sensitivity and responsiveness to
insulin of glucose utilization and hepatic glucose production as
well as the feedback inhibition of endogenous insulin secretion by
insulin. The effect of gonadal steroids on these parameters will
be determined by regression analysis. The sequential multiple
insulin dose euglycemic glucose clamp technique will be used to
define the in vivo dose-response curve to insulin and the modified
frequently sampled intravenous glucose tolerance test will be used
to determine C-peptide metabolism. 2) To Determine the Cellular
Defects in Insulin Action in PCO. This will be accomplished by
investigating in vitro insulin binding and uniformly labeled (14C)-
glucose transport in isolated adipocytes. The effect of gonadal
steroids on these parameters will also be assessed. 3) To
Determine if Decreased Cellular Insulin Binding or Action in PCO
is an Acquired or Intrinsic (? Genetic) Defect. This will be
accomplished by determining whether there are persistent defects
in insulin binding, insulin receptor tyrosine kinase activity,
and/or glucose transport in cultured fibroblasts from PCO women.
StatusFinished
Effective start/end date12/31/897/31/01

Funding

  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

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