MECHANISMS OF INSULIN RESISTANCE IN MAN

  • Rizza, Robert Allan (PI)

Project: Research project

Project Details

Description

The long-term goal of the principal investigator's research is an improved
understanding of glucose metabolism in normal and diabetic man and
ultimately improved therapy of diabetes mellitus. The objective of the
proposed research is to define the roles of insulin and glucose in
regulating hepatic and extrahepatic glucose metabolism in both the
postabsorptive and postprandial states. Isotope dilution techniques will
be central to these studies. Therefore, prior to initiation of these
protocols, the effects of hyperinsulinemia, hyperglycemia, and diabetes
mellitus on "futile" cycling, will be critically examined. Since "futile"
cycling of glucose can alter the validity of these techniques, these
studies will be essential for interpretation of the results of the proposed
research as well as those of all other investigators using these isotopes
in their own research. Subsequently in an effort to establish a firm
scientific basis for the design of appropriate treatment of diabetes
mellitus, the effects of diabetes mellitus on hepatic and extrahepatic
processing of carbohydrate meals will be defined and the ability of
intensive insulin therapy to restore this process towards normal will be
determined. Since diabetes mellitus is characterized by both insulin
resistance and growth hormone excess, the influence of growth hormone on
hepatic and extrahepatic glucose metabolism and meal disposition will be
examined. In order to examine the role of insulin resistance in the
pathogenesis of postprandial glucose intolerance in both NIDDM and IDDM, a
method of assessing insulin action under conditions that mimic those
normally present during meal disposition (i.e., continuously changing
circulating insulin concentrations) will be developed. This method will be
used to measure hepatic and extrahepatic responses to insulin in diabetic
patients. The results obtained will be compared to those observed when
identical amounts of insulin are given as a several hour constant insulin
infusion using the traditional but unphysiologic
hyperinsulinemic-euglycemic clamp. Completion of the proposed protocols
hopefully will provide a better understanding of the mechanisms of glucose
intolerance in diabetes mellitus.
StatusFinished
Effective start/end date5/1/828/31/86

Funding

  • National Institutes of Health

ASJC

  • Medicine(all)

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