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Diazoxide restores beta3-adrenergic receptor function in diet-induced obesity and diabetes.

Publication ,  Journal Article
Surwit, RS; Dixon, TM; Petro, AE; Daniel, KW; Collins, S
Published in: Endocrinology
October 2000

We previously demonstrated that the expression and function of the adipocyte-specific beta3-adrenergic receptor (beta3AR) are significantly depressed in single gene and diet-induced rodent models of obesity. Furthermore, these models are relatively unresponsive to the anti-obesity effects of beta3AR agonists. Because all of these models are hyperinsulinemic, we hypothesized that hyperinsulinemia could be responsible for this abnormality in beta3AR function. The goal of this study was to determine whether lowering insulin with the K-ATP channel agonist, diazoxide (Dz) would reverse the depressed expression and function of the beta3AR found in a model of diet-induced diabetes and obesity in C57BL/6J (B6) mice. B6 male mice were placed on either high fat (HF) or low fat experimental diets. After 4 weeks, HF-fed mice were assigned to a group: HF or HF containing disodium (R,R)-5- [2-( [2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl-1,3-benzodioxole-2,2-di carboxylate (CL; 0.001%, wt/wt), Dz (0.32%, wt/wt), or their combination (CLDz). Dz animals exhibited significantly reduced plasma insulin levels as well as increased 3pAR expression and agonist-stimulated adenylyl cyclase activity in adipocytes. CLDz was more effective in reducing percent body fat, lowering nonesterified fatty acids, improving glucose tolerance, and reducing feed efficiency than either treatment alone.

Duke Scholars

Published In

Endocrinology

DOI

ISSN

0013-7227

Publication Date

October 2000

Volume

141

Issue

10

Start / End Page

3630 / 3637

Location

United States

Related Subject Headings

  • Syndrome
  • Receptors, Adrenergic, beta
  • Organ Size
  • Obesity
  • Muscle, Skeletal
  • Mice, Inbred Strains
  • Mice
  • Male
  • Lipids
  • Leptin
 

Citation

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Chicago
ICMJE
MLA
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Surwit, R. S., Dixon, T. M., Petro, A. E., Daniel, K. W., & Collins, S. (2000). Diazoxide restores beta3-adrenergic receptor function in diet-induced obesity and diabetes. Endocrinology, 141(10), 3630–3637. https://doi.org/10.1210/endo.141.10.7726
Surwit, R. S., T. M. Dixon, A. E. Petro, K. W. Daniel, and S. Collins. “Diazoxide restores beta3-adrenergic receptor function in diet-induced obesity and diabetes.Endocrinology 141, no. 10 (October 2000): 3630–37. https://doi.org/10.1210/endo.141.10.7726.
Surwit RS, Dixon TM, Petro AE, Daniel KW, Collins S. Diazoxide restores beta3-adrenergic receptor function in diet-induced obesity and diabetes. Endocrinology. 2000 Oct;141(10):3630–7.
Surwit, R. S., et al. “Diazoxide restores beta3-adrenergic receptor function in diet-induced obesity and diabetes.Endocrinology, vol. 141, no. 10, Oct. 2000, pp. 3630–37. Pubmed, doi:10.1210/endo.141.10.7726.
Surwit RS, Dixon TM, Petro AE, Daniel KW, Collins S. Diazoxide restores beta3-adrenergic receptor function in diet-induced obesity and diabetes. Endocrinology. 2000 Oct;141(10):3630–3637.
Journal cover image

Published In

Endocrinology

DOI

ISSN

0013-7227

Publication Date

October 2000

Volume

141

Issue

10

Start / End Page

3630 / 3637

Location

United States

Related Subject Headings

  • Syndrome
  • Receptors, Adrenergic, beta
  • Organ Size
  • Obesity
  • Muscle, Skeletal
  • Mice, Inbred Strains
  • Mice
  • Male
  • Lipids
  • Leptin