Effects of prolonged glucose infusion on insulin secretion,
clearance and action in normal subjects.
Boden, Guenther, Jose Ruiz, Cherng-Ju Kim, and Xinhua Chen.
Departments of Medicine (GB, JR, XC) and the General Clinical
Research Center, Temple University Schools of Medicine and Pharmacy
(CJK), Philadelphia, PA 19140
APStracts 2:0199E, 1995.
It was the aim of this study to determine whether prolonged
hyperglycemia can produce _glucose toxicity_ in normal human
subjects. To this end, plasma glucose was clamped at 5, 8.8 and 12.6
mM for 68 h in healthy volunteers. Determined were rates of insulin
secretion (by deconvolution of plasma C-peptide) and rates of insulin
clearance (AUC 24 h insulin secretion/AUC 24 h insulin). Pre- and
post-hyperglycemia glucose turnover was measured (with 6,6 2H2
glucose) during euglycemic-hyperinsulinemic clamping to assess
peripheral (muscle) and hepatic insulin action. Hyperglycemia ( 12.6
mM) for 68 h was associated with significant reductions in rates of
insulin secretion (-35%, p < 0.05), insulin clearance (-57%, p
< 0.05), glucose infusion rates needed to maintain hyperglycemia
(-36%, p < 0.05) and insulin stimulated glucose uptake (-55%, p
< 0.01). No significant changes were seen during 8.8 mM
hyperglycemia or during euglycemia. These data showed that 12.6 mM
hyperglycemia, but not 8.8 mM hyperglycemia or euglycemia, was
associated with reduced insulin secretion, insulin clearance, and
peripheral (muscle) insulin action. We concluded 1) that in normal
subjects desensitization to glucose, involving [beta] cells and
muscle, developed at plasma glucose concentrations of between 9 and
12 mM and 2) that these effects were partially compensated for by a
decrease in insulin clearance.
Received 1 June 1995; accepted in final form 10 August 1995.
APS Manuscript Number E244-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95