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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 the OGTT in normal and STZ rats.Notes: After an 8-hour fast, normal and STZ-induced diabetic mice were intragastrically administered with equal volumes of 0.9% saline or different doses of RA (120, 160, and 200 mg/kg). After 15 minutes, D-glucose (2 g/kg) was orally administered for the OGTT. The results represent the OGTT in (A) normal and (B) diabetic mice, and (C and D) the corresponding calculated relative AUC for glucose concentration. The results are expressed as the means ± SEM (n=8); *P<0.05 and **P<0.01 compared to the control group.Abbreviations: RA, rosmarinic acid; OGTT, oral glucose tolerance test; STZ, streptozocin; AUC, area under the curve; SEM, standard error of the mean.
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f2-dddt-10-2193: Effect of RA on the OGTT in normal and STZ rats.Notes: After an 8-hour fast, normal and STZ-induced diabetic mice were intragastrically administered with equal volumes of 0.9% saline or different doses of RA (120, 160, and 200 mg/kg). After 15 minutes, D-glucose (2 g/kg) was orally administered for the OGTT. The results represent the OGTT in (A) normal and (B) diabetic mice, and (C and D) the corresponding calculated relative AUC for glucose concentration. The results are expressed as the means ± SEM (n=8); *P<0.05 and **P<0.01 compared to the control group.Abbreviations: RA, rosmarinic acid; OGTT, oral glucose tolerance test; STZ, streptozocin; AUC, area under the curve; SEM, standard error of the mean.

Mentions: In pharmacology studies, OGTT was performed after the STZ rats and normal rats were treated with RA (Figure 2) to demonstrate the therapeutic efficiency of RA. The OGTT showed that the maximal blood glucose levels at 30 minutes after glucose administration were 183±5.12 mg/dL in normal rats and 522±11.99 mg/dL in diabetic rats. Pretreatment with RA improved glucose tolerance in a dose-dependent manner (Figure 2A and B) and significantly reduced the calculated relative area under the glucose concentration curve (AUC) (Figure 2C and D) in both normal and diabetic rats.


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 the OGTT in normal and STZ rats.Notes: After an 8-hour fast, normal and STZ-induced diabetic mice were intragastrically administered with equal volumes of 0.9% saline or different doses of RA (120, 160, and 200 mg/kg). After 15 minutes, D-glucose (2 g/kg) was orally administered for the OGTT. The results represent the OGTT in (A) normal and (B) diabetic mice, and (C and D) the corresponding calculated relative AUC for glucose concentration. The results are expressed as the means ± SEM (n=8); *P<0.05 and **P<0.01 compared to the control group.Abbreviations: RA, rosmarinic acid; OGTT, oral glucose tolerance test; STZ, streptozocin; AUC, area under the curve; SEM, standard error of the mean.
© Copyright Policy
Related In: Results  -  Collection

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

f2-dddt-10-2193: Effect of RA on the OGTT in normal and STZ rats.Notes: After an 8-hour fast, normal and STZ-induced diabetic mice were intragastrically administered with equal volumes of 0.9% saline or different doses of RA (120, 160, and 200 mg/kg). After 15 minutes, D-glucose (2 g/kg) was orally administered for the OGTT. The results represent the OGTT in (A) normal and (B) diabetic mice, and (C and D) the corresponding calculated relative AUC for glucose concentration. The results are expressed as the means ± SEM (n=8); *P<0.05 and **P<0.01 compared to the control group.Abbreviations: RA, rosmarinic acid; OGTT, oral glucose tolerance test; STZ, streptozocin; AUC, area under the curve; SEM, standard error of the mean.
Mentions: In pharmacology studies, OGTT was performed after the STZ rats and normal rats were treated with RA (Figure 2) to demonstrate the therapeutic efficiency of RA. The OGTT showed that the maximal blood glucose levels at 30 minutes after glucose administration were 183±5.12 mg/dL in normal rats and 522±11.99 mg/dL in diabetic rats. Pretreatment with RA improved glucose tolerance in a dose-dependent manner (Figure 2A and B) and significantly reduced the calculated relative area under the glucose concentration curve (AUC) (Figure 2C and D) in both normal and diabetic rats.

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