Document Detail

Mechanism, temporal patterns, and magnitudes of the metabolic responses to the KATP channel agonist diazoxide.
MedLine Citation:
PMID:  15339745     Owner:  NLM     Status:  MEDLINE    
To assess the mechanism, temporal patterns, and magnitudes of the metabolic responses to the ATP-dependent potassium channel agonist diazoxide, neuroendocrine and metabolic responses to intravenous diazoxide (saline, 1.0 and 2.0 mg/kg) and oral diazoxide (placebo, 4.0 and 6.0 mg/kg) were assessed in healthy young adults. Intravenous diazoxide produced rapid, but transient, decrements (P = 0.0023) in plasma insulin (e.g., nadirs of 2.8 +/- 0.5 and 1.8 +/- 0.3 microU/ml compared with 7.0 +/- 1.0 microU/ml after saline at 4.0-7.5 min) and C-peptide (P = 0.0228) associated with dose-related increments in plasma glucose (P = 0.0044) and serum nonesterified fatty acids (P < 0.0001). After oral diazoxide, plasma insulin appeared to decline, as did C-peptide, again associated with dose-related increments in plasma glucose (P < 0.0001) and serum nonesterified fatty acids (P = 0.0141). Plasma glucagon, as well as cortisol and growth hormone, was not altered. Plasma epinephrine increased (P = 0.0215) slightly only after intravenous diazoxide. There were dose-related increments in plasma norepinephrine (P = 0.0038 and P = 0.0005, respectively), undoubtedly reflecting a compensatory sympathetic neural response to vasodilation produced by diazoxide, but these would not raise plasma glucose or serum nonesterified fatty acid levels. Thus selective suppression of insulin secretion, without stimulation of glucagon secretion, raised plasma glucose and serum nonesterified fatty acid concentrations. These findings define the temporal patterns and magnitudes of the metabolic responses to diazoxide and underscore the primacy of regulated insulin secretion in the physiological regulation of postabsorptive carbohydrate and lipid metabolism.
Bharathi Raju; Philip E Cryer
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-08-31
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  288     ISSN:  0193-1849     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2004-12-08     Completed Date:  2005-03-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E80-5     Citation Subset:  IM    
Division of Endocrinology, Metabolism, and Lipid Research, The General Clinical Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.
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MeSH Terms
Adenosine Triphosphate / metabolism
Administration, Oral
Blood Glucose / drug effects,  metabolism
Diazoxide / administration & dosage*
Epinephrine / blood
Fatty Acids, Nonesterified / blood
Glucagon / blood,  secretion
Injections, Intravenous
Insulin / blood,  secretion*
Potassium Channels / agonists*,  physiology
Vasodilator Agents / administration & dosage*
Grant Support
Reg. No./Substance:
0/Blood Glucose; 0/Fatty Acids, Nonesterified; 0/Potassium Channels; 0/Vasodilator Agents; 11061-68-0/Insulin; 364-98-7/Diazoxide; 51-43-4/Epinephrine; 56-65-5/Adenosine Triphosphate; 9007-92-5/Glucagon

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