TESTOSTERONE-INDUCED INSULIN INSENSITIVITY

Project: Research project

Description

Hyperandrogenism and insulin resistance frequently coexist,
although the cause and effect relationship of this association is
not clear. The possibility that hyperandrogenism may induce
insulin insensitivity, with resultant hyperinsulinemia, has become
of increased clinical importance. This heightened significance
stems from epidemiologic reports suggesting a link of
hyperinsulinism with atherosclerosis and coronary vascular disease. Examination of the effect of androgens on insulin sensitivity has
primarily utilized glucose tolerance testing. Our preliminary
studies have utilized "clamp" methodologies which fix glucose or
glucose and insulin concentrations at predetermined levels, thereby
minimizing homeostatic responses and allowing evaluation of the
effect of each individual parameter. In our studies,
methyltestosterone administration resulted in a reduction in
insulin sensitivity in normal women, when assessed either by the
euglycemic, hyperinsulinemic clamp technique or the hyperglycemic
clamp technique. Furthermore, testosterone administration markedly
reduced glucose uptake in dogs during euglycemic, hyperinsulinemic
clamp studies. This protocol will test the hypothesis suggested by these three
studies, namely that testosterone induces insulin insensitivity.
The proposal will evaluate insulin sensitivity after elevation or
reduction of testosterone levels in humans and animals. The
techniques to be utilized are l) euglycemic, hyperinsulinemic clamp
studies in association with 3-3H-glucose and L-[l-13C)leucine
infusion and the performance of indirect calorimetry, 2)
hyperglycemic clamp procedures, and 3) 24h whole body calorimetry
studies. The mechanism of testosterone action will be assessed by
indirect calorimetry to determine the fate of glucose and leucine
taken up by muscle (either oxidation or storage). Lastly, this
proposal will examine the sexual dimorphism that exists with regard
to the ability of testosterone to reduce insulin sensitivity in
women, but not in men in whom testosterone levels are several-fold
higher.
StatusFinished
Effective start/end date5/1/944/30/99

Funding

  • National Institutes of Health: $167,565.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $173,654.00

Fingerprint

Testosterone
Insulin
Insulin Resistance
Glucose
Hyperandrogenism
Indirect Calorimetry
Hyperinsulinism
Glucose Clamp Technique
Methyltestosterone
Calorimetry
Vascular Diseases
Sex Characteristics
Androgens
Coronary Disease
Atherosclerosis
Leucine
Dogs
Muscles

ASJC

  • Medicine(all)