Project: Research project

Project Details


Our previous studies have examined various aspects of splanchnic, hepatic,
and peripheral glucose metabolism in normal and diabetic subjects. The
present studies will extend these initial observations as follows: The effect of insulin on peripheral (femoral vein catheter), splanchnic
(hepatic vein catheter), and hepatic (3H-3-glucose) glucose metabolism will
be examined susing the insulin clamp technique in healthy controls, normal
weight non-insulin-dependent diabetics (NIDD), obese NIDD, and IDD with
varying degrees of hyperglycemia. In all subjects beta cell secretory
function will also be examined with the hyperglycemic clamp technique and
the oral glucose tolerance test. Abnormalities in insulin-mediated glucose
metabolism will be related to existing defects in insulin secretion in the
same individual. The ability of glyburide, conventional insulin treatment,
insulin pump therapy, and exercise to enhance tissue sensitivity to insulin
in the preceeding groups will be evaluated. Using a) insulin binding to
monocytes, b) examination of the shape of the dose response curve relating
the plasma insulin concentration to glucose uptake, and c) indirect
calorimetry to measure glucose oxidation (and intracellular process), an
attempt will be made to define the contribution of receptor versus
postreceptor defects to the impairment in insulin action. It is hoped that
such analysis will provide insight as to how various therapeutic modalities
are capable of enhancing tissue sensitivity to insulin. Separate studies
will be performed in NIDD and IDD using a double tracer technique
(3H-3-glucose and 14C-glucose) in combination with hepatic vein
catheterization to quantitate splanchnic glucose uptake and suppression of
hepatic glucose production following oral glucose. These studies will be
performed in combination with indirect calorimetry to simultaneously
quantitate glucose oxidation and glucose storage. The oral glucose load
will be repeated after glyburide or insulin (NIDD) and after insulin pump
(IDD) therapy. In additional studies various aspects of dietary-induced
thermogenesis will be examined in control, obese, and NIDD subjects before
and after weight reduction.
Effective start/end date9/15/7811/30/88


  • National Institutes of Health


  • Medicine(all)


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