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

Ramin Alemzadeh, Jian Zhang, Kathryn Tushaus, John Koontz

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalMedical Science Monitor
Volume10
Issue number3
StatePublished - Mar 1 2004
Externally publishedYes

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Diazoxide
Zucker Rats
Proto-Oncogene Proteins c-akt
Facilitative Glucose Transport Proteins
Adipose Tissue
Insulin Receptor Substrate Proteins
Hyperinsulinism
Insulin
Adipocytes
Messenger RNA
Proteins
Glucose
Genes
Insulin Resistance
Gene Expression

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Diazoxide enhances adipose tissue protein kinase B activation and gluclose transporter-4 expression in obese Zucker rats. / Alemzadeh, Ramin; Zhang, Jian; Tushaus, Kathryn; Koontz, John.

In: Medical Science Monitor, Vol. 10, No. 3, 01.03.2004.

Research output: Contribution to journalArticle

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title = "Diazoxide enhances adipose tissue protein kinase B activation and gluclose transporter-4 expression in obese Zucker rats",
abstract = "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.",
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N2 - 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.

AB - 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.

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