Costus pictus D. Don leaf extract stimulates GLP-1 secretion from GLUTag L-cells and has cytoprotective effects in BRIN-BD11 β-cells. (5th October 2020)

• Record Type: Journal Article
• Authors: Patibandla, Chinmai; Khan, Zahidul Islam; MacGregor, Louise; Campbell, Mark James; Patterson, Steven
• Is Part Of: Journal of ethnopharmacology. Volume 260(2020)
• Publication Date: 2020-10-05
• Subjects: GLP-1 -- Costus pictus -- β-Cell -- L-cell -- Cytoprotection; GLP-1 Glucagon-like peptide 1 -- T2DM Type 2 Diabetes Mellitus -- CPE Costus pictus extract -- CP Costus pictus -- ROS reactive oxygen species -- Nrf2 Nuclear Factor Erythroid 2 Like 2 -- Sod Superoxide dismutase -- Cat Catalase -- Gpx1 Glutathione peroxidase 1 -- Nfkb Nuclear Factor Kappa B Subunit -- Myc Proto-Oncogene C-Myc -- Erk Extracellular Signal-Regulated Kinase -- Jnk1 C-Jun N-terminal kinase 1 -- C-Jun Jun Proto-Oncogene -- Ins1 Insulin1 -- Pdx1 Pancreatic And Duodenal Homeobox 1 -- MafA MAF BZIP Transcription Factor A -- Gck Glucokinase -- Pc1/Pcsk1 Prohormone convertase 1 -- Pc2/Pcsk2 Prohormone convertase 2 -- Gcg Proglucagon -- Sglt1 Sodium/Glucose Cotransporter 1; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2020.112970
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Costus pictus D. Don, commonly known as insulin plant, is a traditional Indian antidiabetic herbal medicine with glucose-lowering and insulin secretory effects having been reported in animal models and humans with Type 2 diabetes. However, its effects on GLP-1 secretion from intestinal endocrine L-cells and potential metabolic and protective effects in insulin secreting pancreatic β-cells are not yet fully understood. Aim of the study: This study is aimed to elucidate the effects of Costus pictus D. Don leaf extract (CPE) on L-cell function and GLP-1 secretion using the established murine GLUTag L-cell model and to investigate its potential cytoprotective effects against detrimental effects of palmitate and cytokines in pancreatic β-cells using BRIN-BD11 cells. Methods: Costus pictus D. Don dried leaf powder was extracted by soxhlet method. Cell viability was determined by MTT assay. Changes in gene and protein expression were quantified by qPCR and western blotting, respectively. GLP-1 and insulin secretion were measured by ELISA. Results: CPE significantly enhanced the percentage of viable BRIN-BD11 and GLUTag cells and protected BRIN-BD11 cells against palmitate- and proinflammatory cytokine-induced toxicity. CPE enhanced acute GLP-1 secretion 6.4–16.3-fold from GLUTag cells at both low (1.1 mM) and high (16.7 mM) glucose (P < 0.01) concentrations. Antioxidant (Nrf2, Cat & Gpx1) and pro-proliferative (Erk1 and Jnk1) gene expression were upregulated by 24 h culture with CPE, while proinflammatory transcription factor NF-κB was downregulated. Conclusion: Diminished postprandial GLP-1 secretion and loss of insulin secreting β-cells are known contributors of T2DM. Our data suggests that CPE acutely stimulates GLP-1 secretion from L-cells. Long term exposure of the BRIN-BD11 cells to CPE enhances cell number and may protect against palmitate and proinflammatory cytokines by activating multiple pathways. Thus, the current study suggests that the possible antidiabetic properties of CPE may be linked to enhanced GLP-1 secretion and β-cell protection which could be beneficial in the management of T2DM. Graphical abstract: Image 1