REGULATION OF FFA METABOLISM IN NORMAL AND DIABETIC MAN

  • Miles, John M (PI)

Project: Research project

Project Details

Description

This research will continue in the area of regulation of lipolysis
and free fatty acid oxidation in humans. An extremely precise
and accurate high performance liquid chromatographic method for
the determination of plasma palmitate concentration and specific
activity has been developed and its accuracy validated. The
proposed studies will systematically investigate the hormonal and
substrate factors which regulate lipolysis and free fatty acid
oxidation, using the "pancreatic clamp" technique. While
extensive in vitro information on this subject is available, the
hormone and substrate factors which regulate the mobilization
and oxidation of free fatty acids remain to be determined. The
proposal will focus initially on the dose-response relationship
between insulin availability and free fatty acid mobilization and
oxidation during infusion of insulin at rates which will achieve
circulating plasma concentrations between 5 and 50 Mu/ml. On
the basis of the results from these experiments, an insulin infusion
rate will be selected for subsequent studies to independently
assess the effects of graded hyperglycemia and incremental
increases, within the physiologic range, of epinephrine, growth
hormone, glucagon and cortisol in normal subjects and insulin-
dependent diabetics. Specifically, these studies will 1) determine
whether the sensitivity and/or responsiveness of lipolysis and free
fatty acid oxidation is reduced in poorly controlled insulin-
dependent diabetes; 2) determine whether hyperglycemia per se
inhibits lipolysis and/or free fatty acid oxidation in normal and
diabetic man; 3) determine whether the sensitivity and
responsiveness of lipolysis and free fatty acid oxidation to
epinephrine is normal or increased in poorly controlled diabetes;
4) determine whether growth hormone excess increases lipolysis
and free fatty acid oxidation in normal and diabetic man; 5)
determine whether glucagon stimulates lipolysis and free fatty
acid oxidation in normal and diabetic man; and 6) determine
whether hypercortisolemia increases lipolysis in normal subjects
and patients with poorly controlled diabetes. These studies will
provide new insights into the control of free fatty acid
metabolism in vivo and will lead to additional studies of the
effect of substrate and hormonal interactions in the regulation of
fuel metabolism in man.
StatusFinished
Effective start/end date12/1/868/31/98

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $198,900.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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