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Abstract
The mechanism of action of diazoxide vas investigated in dogs. Immunoreactive insulin,
glucose, and free fatty acids were determined in treated and control dogs following
intravenously administered glucose. The slower disappearance of glucose in the treated
animals was associated with almost complete IRI suppression. Alpha adrenergic receptor
blockade with phentolamine prevented the diabetogenic and insulin suppressive effects
of diazoxide. Experiments in fasting dogs demonstrated that the elevation of FFA which
follows diazoxide administration can be largely inhibited by beta adrenergic blockade
with propranolol. The metabolic effects of diazoxide are therefore mediated either
directly or indirectly through alpha and beta adrenergic receptors. Additional experiments
indicated that the diazoxide effect on glucose tolerance and insulin secretion is
not blocked by pretreatment with reserpine. Treatment with the massive doses of reserpine
necessary to deplete tissue catecholamines caused a near-moribund state. However,
the diazoxide effect could be demonstrated in the reserpinized animals that maintained
the ability to secrete insulin normally in response to a glucose load. Our findings
suggest that diazoxide stimulates alpha and beta adrenergic receptors directly.
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Article info
Publication history
Accepted:
January 20,
1967
Received:
November 15,
1966
Footnotes
☆Supported by Research Grant AM 10151-01, National Institute of Arthritis and Metabolic Diseases, United States Public Health Service.
Identification
Copyright
© 1967 Published by Elsevier Inc.