Mechanisms of dexamethasone-induced insulin resistance in healthy humans

Details

Serval ID
serval:BIB_B3443B6036D2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mechanisms of dexamethasone-induced insulin resistance in healthy humans
Journal
Journal of Clinical Endocrinology and Metabolism
Author(s)
Tappy  L., Randin  D., Vollenweider  P., Vollenweider  L., Paquot  N., Scherrer  U., Schneiter  P., Nicod  P., Jequier  E.
ISSN
0021-972X (Print)
Publication state
Published
Issued date
10/1994
Volume
79
Number
4
Pages
1063-9
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Oct
Abstract
Insulin resistance may result from decreased muscle blood flow, impaired cellular glucose transport, or intracellular deficits of glucose metabolism. The mechanisms responsible for dexamethasone-induced insulin resistance were investigated in healthy human subjects. During a 2-h hyperinsulinemic clamp, dexamethasone decreased glucose uptake, oxidation, and nonoxidative glucose disposal during the first hour. During the second hour, glucose uptake was normalized by means of hyperglycemia; glucose oxidation, however, remained suppressed by dexamethasone. Dexamethasone also abolished the insulin-mediated increase in calf blood flow. When acipimox was administered during the clamps to correct glucocorticoid-induced inhibition of glucose oxidation, dexamethasone decreased whole body glucose uptake and nonoxidative glucose disposal in the same proportion as when no acipimox was administered. However, glucose oxidation and insulin-mediated calf blood flow were normalized after acipimox. During the second hour, exogenous glucose infusion was matched to that used in the control clamp and normalized whole body glucose uptake. However, hyperglycemia developed, indicating insulin resistance. It is concluded that dexamethasone 1) decreases glucose oxidation independently of glucose transport; this inhibition is reversed by acipimox; and 2) decreases whole body glucose uptake independently of increased lipolysis, decreased glucose oxidation, or an altered muscle blood flow.
Keywords
Adult Antilipemic Agents/pharmacology Blood Glucose/analysis Dexamethasone/*pharmacology Female Glucose/metabolism Glucose Clamp Technique Humans Insulin/blood *Insulin Resistance Leg/blood supply Male Oxidation-Reduction/drug effects Pyrazines/pharmacology Regional Blood Flow/drug effects
Pubmed
Web of science
Create date
24/01/2008 13:36
Last modification date
20/08/2019 15:21
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