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Rosmarinic acid ameliorates hyperglycemia and insulin sensitivity in diabetic rats, potentially by modulating the expression of PEPCK and GLUT4.

Runtuwene J, Cheng KC, Asakawa A, Amitani H, Amitani M, Morinaga A, Takimoto Y, Kairupan BH, Inui A - Drug Des Devel Ther (2016)

Bottom Line: These effects of RA were dose-dependent.Meanwhile, RA administration reversed the STZ- and HFD-induced increase in PEPCK expression in the liver and the STZ- and HFD-induced decrease in GLUT4 expression in skeletal muscle.RA reduces hyperglycemia and ameliorates insulin sensitivity by decreasing PEPCK expression and increasing GLUT4 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia.

ABSTRACT

Background: Rosmarinic acid (RA) is a natural substance that may be useful for treating diabetes mellitus. The present study investigated the effects of RA on glucose homeostasis and insulin regulation in rats with streptozocin (STZ)-induced type 1 diabetes or high-fat diet (HFD)-induced type 2 diabetes.

Methods: Glucose homeostasis was determined using oral glucose tolerance tests and postprandial glucose tests, and insulin activity was evaluated using insulin tolerance tests and the homeostatic model assessment for insulin resistance. Additionally, the protein expression levels of PEPCK and GLUT4 were determined using Western blot analysis.

Results: RA administration exerted a marked hypoglycemic effect on STZ-induced diabetic rats and enhanced glucose utilization and insulin sensitivity in HFD-fed diabetic rats. These effects of RA were dose-dependent. Meanwhile, RA administration reversed the STZ- and HFD-induced increase in PEPCK expression in the liver and the STZ- and HFD-induced decrease in GLUT4 expression in skeletal muscle.

Conclusion: RA reduces hyperglycemia and ameliorates insulin sensitivity by decreasing PEPCK expression and increasing GLUT4 expression.

No MeSH data available.


Related in: MedlinePlus

Effect of RA on PEPCK protein levels in the liver and GLUT4 protein levels in the skeletal muscle in HFD rats.Notes: Sample extracts were prepared from the NC, HFD, and HFD + RA groups. HFD rats were treated with RA (200 mg/kg) via intraperitoneal injection for 7 days. (A) PEPCK expression levels in the liver. (B) Immunoblots showing GLUT4 levels in the cytosol and membrane fractions of skeletal muscle samples. The GLUT4 protein level in rats fed control chow was used as the control for the relevant quantifications. Each bar represents the mean ± SEM (n=6). *P<0.05 vs NC and #P<0.05 vs HFD.Abbreviations: RA, rosmarinic acid; HFD, high-fat diet; NC, normal control; SEM, standard error of the mean.
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f6-dddt-10-2193: Effect of RA on PEPCK protein levels in the liver and GLUT4 protein levels in the skeletal muscle in HFD rats.Notes: Sample extracts were prepared from the NC, HFD, and HFD + RA groups. HFD rats were treated with RA (200 mg/kg) via intraperitoneal injection for 7 days. (A) PEPCK expression levels in the liver. (B) Immunoblots showing GLUT4 levels in the cytosol and membrane fractions of skeletal muscle samples. The GLUT4 protein level in rats fed control chow was used as the control for the relevant quantifications. Each bar represents the mean ± SEM (n=6). *P<0.05 vs NC and #P<0.05 vs HFD.Abbreviations: RA, rosmarinic acid; HFD, high-fat diet; NC, normal control; SEM, standard error of the mean.

Mentions: The protein expression levels of PEPCK and GLUT4 were analyzed in STZ-induced diabetic rats and HFD-fed diabetic rats using Western blot analysis. PEPCK expression was markedly increased in isolated liver cells (Figures 5 and 6) in both the STZ-induced diabetic rats and the HFD-fed diabetic rats. RA treatment reduced hepatic PEPCK expression in both groups, suggesting that RA increased gluconeogenesis in the livers of diabetic rats. However, the decrease in PEPCK levels in the STZ group was more significant than the decrease in the HFD group. Additionally, we examined GLUT4 protein expression in muscle tissues to explore changes in glucose uptake (Figure 6), and we found that GLUT4 expression was significantly lower in both the STZ-induced diabetic rats and the HFD-fed diabetic rats. RA treatment markedly increased GLUT4 expression in both groups. Therefore, RA increased GLUT4 expression in skeletal muscle.


Rosmarinic acid ameliorates hyperglycemia and insulin sensitivity in diabetic rats, potentially by modulating the expression of PEPCK and GLUT4.

Runtuwene J, Cheng KC, Asakawa A, Amitani H, Amitani M, Morinaga A, Takimoto Y, Kairupan BH, Inui A - Drug Des Devel Ther (2016)

Effect of RA on PEPCK protein levels in the liver and GLUT4 protein levels in the skeletal muscle in HFD rats.Notes: Sample extracts were prepared from the NC, HFD, and HFD + RA groups. HFD rats were treated with RA (200 mg/kg) via intraperitoneal injection for 7 days. (A) PEPCK expression levels in the liver. (B) Immunoblots showing GLUT4 levels in the cytosol and membrane fractions of skeletal muscle samples. The GLUT4 protein level in rats fed control chow was used as the control for the relevant quantifications. Each bar represents the mean ± SEM (n=6). *P<0.05 vs NC and #P<0.05 vs HFD.Abbreviations: RA, rosmarinic acid; HFD, high-fat diet; NC, normal control; SEM, standard error of the mean.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4940010&req=5

f6-dddt-10-2193: Effect of RA on PEPCK protein levels in the liver and GLUT4 protein levels in the skeletal muscle in HFD rats.Notes: Sample extracts were prepared from the NC, HFD, and HFD + RA groups. HFD rats were treated with RA (200 mg/kg) via intraperitoneal injection for 7 days. (A) PEPCK expression levels in the liver. (B) Immunoblots showing GLUT4 levels in the cytosol and membrane fractions of skeletal muscle samples. The GLUT4 protein level in rats fed control chow was used as the control for the relevant quantifications. Each bar represents the mean ± SEM (n=6). *P<0.05 vs NC and #P<0.05 vs HFD.Abbreviations: RA, rosmarinic acid; HFD, high-fat diet; NC, normal control; SEM, standard error of the mean.
Mentions: The protein expression levels of PEPCK and GLUT4 were analyzed in STZ-induced diabetic rats and HFD-fed diabetic rats using Western blot analysis. PEPCK expression was markedly increased in isolated liver cells (Figures 5 and 6) in both the STZ-induced diabetic rats and the HFD-fed diabetic rats. RA treatment reduced hepatic PEPCK expression in both groups, suggesting that RA increased gluconeogenesis in the livers of diabetic rats. However, the decrease in PEPCK levels in the STZ group was more significant than the decrease in the HFD group. Additionally, we examined GLUT4 protein expression in muscle tissues to explore changes in glucose uptake (Figure 6), and we found that GLUT4 expression was significantly lower in both the STZ-induced diabetic rats and the HFD-fed diabetic rats. RA treatment markedly increased GLUT4 expression in both groups. Therefore, RA increased GLUT4 expression in skeletal muscle.

Bottom Line: These effects of RA were dose-dependent.Meanwhile, RA administration reversed the STZ- and HFD-induced increase in PEPCK expression in the liver and the STZ- and HFD-induced decrease in GLUT4 expression in skeletal muscle.RA reduces hyperglycemia and ameliorates insulin sensitivity by decreasing PEPCK expression and increasing GLUT4 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia.

ABSTRACT

Background: Rosmarinic acid (RA) is a natural substance that may be useful for treating diabetes mellitus. The present study investigated the effects of RA on glucose homeostasis and insulin regulation in rats with streptozocin (STZ)-induced type 1 diabetes or high-fat diet (HFD)-induced type 2 diabetes.

Methods: Glucose homeostasis was determined using oral glucose tolerance tests and postprandial glucose tests, and insulin activity was evaluated using insulin tolerance tests and the homeostatic model assessment for insulin resistance. Additionally, the protein expression levels of PEPCK and GLUT4 were determined using Western blot analysis.

Results: RA administration exerted a marked hypoglycemic effect on STZ-induced diabetic rats and enhanced glucose utilization and insulin sensitivity in HFD-fed diabetic rats. These effects of RA were dose-dependent. Meanwhile, RA administration reversed the STZ- and HFD-induced increase in PEPCK expression in the liver and the STZ- and HFD-induced decrease in GLUT4 expression in skeletal muscle.

Conclusion: RA reduces hyperglycemia and ameliorates insulin sensitivity by decreasing PEPCK expression and increasing GLUT4 expression.

No MeSH data available.


Related in: MedlinePlus