RGD Reference Report - Diazoxide restores beta3-adrenergic receptor function in diet-induced obesity and diabetes. - Rat Genome Database

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

Authors: Surwit, RS  Dixon, TM  Petro, AE  Daniel, KW  Collins, S 
Citation: Surwit RS, etal., Endocrinology. 2000 Oct;141(10):3630-7.
RGD ID: 2313165
Pubmed: PMID:11014217   (View Abstract at PubMed)
DOI: DOI:10.1210/endo.141.10.7726   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ADRB3Humanhyperinsulinism  ISOAdrb3 (Mus musculus)associated with Obesity more ...RGD 
Adrb3Rathyperinsulinism  ISOAdrb3 (Mus musculus)associated with Obesity more ...RGD 
Adrb3Mousehyperinsulinism  IEP associated with Obesity more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Adrb3  (adrenoceptor beta 3)

Genes (Mus musculus)
Adrb3  (adrenergic receptor, beta 3)

Genes (Homo sapiens)
ADRB3  (adrenoceptor beta 3)


Additional Information