RGD Reference Report - Diazoxide enhances adipose tissue protein kinase B activation and glucose transporter-4 expression in obese Zucker rats. - Rat Genome Database

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Diazoxide enhances adipose tissue protein kinase B activation and glucose transporter-4 expression in obese Zucker rats.

Authors: Alemzadeh, R  Zhang, J  Tushaus, K  Koontz, J 
Citation: Alemzadeh R, etal., Med Sci Monit 2004 Mar;10(3):BR53-60. Epub 2004 Mar 1.
RGD ID: 1354694
Pubmed: PMID:14976464   (View Abstract at PubMed)

BACKGROUND: Attenuation of hyperinsulinemia in obese Zucker rats by diazoxide (DZ) enhanced insulin sensitivity and insulin-stimulated glucose uptake in isolated adipocytes. To determine if these metabolic effects are due to changes in glucose transporter (Glut)-4 gene products and intracellular signaling, we studied the effects DZ on adipose tissue Glut-4 gene products, insulin receptor substrate (IRS)-1, total and phosphorylated protein kinase B (PKB)/Akt. MATERIAL/METHODS: DZ (150 mg/kg per day) or vehicle (control) was administered to 7-week-old female obese and lean Zucker rats for 6 weeks. RESULTS: While adipose Glut-4 mRNA levels from control obese and lean rats were similar, Glut-4 protein content was 60% lower in obese than lean animals (p<0.05). DZ treatment increased mRNA in both obese (1.4 fold) and lean (1.7 fold) animals compared to controls (p<0.05), which was associated with a 3.7 fold and a 1.4 fold increase in Glut-4 protein content in DZ obese (p<0.01) and lean (p<0.05) rats, respectively. IRS-1 protein expression was lower in obese compared to lean rats (p<0.01) and was enhanced in DZ-treated obese (p<0.02) and lean (p<0.05) rats. While the PKB/Akt protein levels were similar in both strains, obese had lower p-Akt levels than lean rats (p<0.01). DZ-treated obese and lean rats had higher levels of p-Akt than their controls (p<0.05). CONCLUSIONS: Chronic suppression of hyperinsulinemia in obese Zucker rats improved intracellular insulin signaling and Glut-4 gene expression, corresponding to enhanced glucose uptake in isolated adipocytes. The discrepancy between adipose tissue Glut-4 mRNA and protein content in response to DZ treatment suggests post-transcriptional regulatory effects resulting from enhanced metabolic efficiency of insulin action.



Objects referenced in this article
Strain Crl:ZUC-Leprfa Zucker rats Rattus norvegicus

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