BMC Complementary and Alternative Medicine | |
[6]-Gingerol, from Zingiber officinale, potentiates GLP-1 mediated glucose-stimulated insulin secretion pathway in pancreatic β-cells and increases RAB8/RAB10-regulated membrane presentation of GLUT4 transporters in skeletal muscle to improve hyperglycemia in Leprdb/db type 2 diabetic mice | |
Research Article | |
Md. Nurul Absar Bin Mohsin1  Farjana Akhter1  Naziat Unnoor1  Bodiul Alam Razu1  Mohammad Tashnim Hossain1  Sinayat Mahzabeen2  J. M. A. Hannan3  Ishrat Aklima Muna4  Ashraf Ul Kabir5  Mehdi Bin Samad6  | |
[1] Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh;Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh;Department of Pharmacy, BRAC University, Dhaka, Bangladesh;Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh;Department of Pharmacy, East West University, Dhaka, Bangladesh;Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh;Seoul National University, Seoul, South Korea;Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh;Washington University School of Medicine in St. Louis, St. Louis, MO, USA;Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA;Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh; | |
关键词: [6]-Gingerol; Lepr mice; Type 2 diabetes; GLP-1; Rab27a; GLUT4; Glycogen synthase 1; Rab8; Rab10; | |
DOI : 10.1186/s12906-017-1903-0 | |
received in 2017-04-09, accepted in 2017-08-02, 发布年份 2017 | |
来源: Springer | |
【 摘 要 】
Background[6]-Gingerol, a major component of Zingiber officinale, was previously reported to ameliorate hyperglycemia in type 2 diabetic mice. Endocrine signaling is involved in insulin secretion and is perturbed in db/db Type-2 diabetic mice. [6]-Gingerol was reported to restore the disrupted endocrine signaling in rodents. In this current study on Leprdb/db diabetic mice, we investigated the involvement of endocrine pathway in the insulin secretagogue activity of [6]-Gingerol and the mechanism(s) through which [6]-Gingerol ameliorates hyperglycemia.MethodsLeprdb/db type 2 diabetic mice were orally administered a daily dose of [6]-Gingerol (200 mg/kg) for 28 days. We measured the plasma levels of different endocrine hormones in fasting and fed conditions. GLP-1 levels were modulated using pharmacological approaches, and cAMP/PKA pathway for insulin secretion was assessed by qRT-PCR and ELISA in isolated pancreatic islets. Total skeletal muscle and its membrane fractions were used to measure glycogen synthase 1 level and Glut4 expression and protein levels.Results4-weeks treatment of [6]-Gingerol dramatically increased glucose-stimulated insulin secretion and improved glucose tolerance. Plasma GLP-1 was found to be significantly elevated in the treated mice. Pharmacological intervention of GLP-1 levels regulated the effect of [6]-Gingerol on insulin secretion. Mechanistically, [6]-Gingerol treatment upregulated and activated cAMP, PKA, and CREB in the pancreatic islets, which are critical components of GLP-1-mediated insulin secretion pathway. [6]-Gingerol upregulated both Rab27a GTPase and its effector protein Slp4-a expression in isolated islets, which regulates the exocytosis of insulin-containing dense-core granules. [6]-Gingerol treatment improved skeletal glycogen storage by increased glycogen synthase 1 activity. Additionally, GLUT4 transporters were highly abundant in the membrane of the skeletal myocytes, which could be explained by the increased expression of Rab8 and Rab10 GTPases that are responsible for GLUT4 vesicle fusion to the membrane.ConclusionsCollectively, our study reports that GLP-1 mediates the insulinotropic activity of [6]-Gingerol, and [6]-Gingerol treatment facilitates glucose disposal in skeletal muscles through increased activity of glycogen synthase 1 and enhanced cell surface presentation of GLUT4 transporters.
【 授权许可】
CC BY
© The Author(s). 2017
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO202311093936243ZK.pdf | 7108KB | download |
【 参考文献 】
- [1]
- [2]
- [3]
- [4]
- [5]
- [6]
- [7]
- [8]
- [9]
- [10]
- [11]
- [12]
- [13]
- [14]
- [15]
- [16]
- [17]
- [18]
- [19]
- [20]
- [21]
- [22]
- [23]
- [24]
- [25]
- [26]
- [27]
- [28]
- [29]
- [30]
- [31]
- [32]
- [33]
- [34]
- [35]
- [36]
- [37]
- [38]
- [39]
- [40]
- [41]
- [42]
- [43]
- [44]
- [45]
- [46]
- [47]
- [48]