Abstract
Glucagon-like peptide 1 (GLP-1) is an incretin hormone produced in gut L-cells, which regulates postprandial glucose-dependent insulin secretion, also known as the incretin effect. GLP-1 secretion may be reduced in type 2 diabetes mellitus, impacting on glycaemic regulation. Thus, methods to enhance endogenous GLP-1 secretion by use of natural GLP-1 secretagogues may improve glucose control in diabetes. Gypenosides (GYP) extracted from the plant Gynostemma Pentaphyllum (Jiaogulan) are known for their glucose-lowering effects both in vitro and in vivo, although their effect on GLP-1 secretion is unknown. Our results showed that GYP enhanced cell viability and significantly upregulated antioxidant gene Nrf2, Cat and Ho-1 expression. GYP did not affect glucokinase expression but downregulated proglucagon gene expression over 24h, although, cellular GLP-1 content was unchanged. Prohormone convertase 1 (Pcsk1) gene expression was unchanged by GYP over 24h, although protein levels were significantly downregulated, while prohormone convertase 2 (Pcsk2) mRNA and protein levels were significantly upregulated. Acute exposure to gypenosides enhanced calcium uptake and GLP-1 release from GLUTag cells both at low and high glucose concentrations. These results suggest that anti-diabetic properties of gypenosides are partly linked to their ability to stimulate GLP-1 secretion. Gypenosides enhance antioxidant gene expression and may protect L-cells from excess oxidative stress.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Authors’ email addresses: Chinmai Patibandla (cpatib10{at}gcu.ac.uk); Erin Campbell (ecampb205{at}caledonian.ac.uk); Xinhua Shu (Xinhua.Shu{at}gcu.ac.uk); Angus M Shaw (angusmshaw65{at}gmail.com); Sharron Dolan (sharron.dolan{at}gcu.ac.uk);
Abbreviations
- GLP-1
- Glucagon-like peptide-1
- GYP
- Gypenosides
- T2DM
- Type 2 diabetes mellitus
- Ncx
- Sodium/Calcium exchange channel
- Sglt1
- Sodium/glucose cotransporter 1
- Gcg
- Glucagon
- Gck
- Glucokinase
- Pc1
- Prohormone convertase-1
- Pc2
- Prohormone convertase-2
- Nrf2
- Nuclear factor erythroid 2-related factor 2
- NFkb1
- Nuclear factor Kappa b1
- Cat
- Catalase
- Ho-1
- Heme oxygenase-1
- MTT
- 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide