The roles of coffee derivatives in pancreatic beta cell survival and function in type 2 diabetes

Abstract

Non-caffeinated coffee derivatives such as chlorogenic acids (CGAs), cafestol CFT) and trigonelline (TRG) have been shown to reduce the risk of type 2 diabetes (T2D). However, it is unclear whether the derivatives directly affect pancreatic beta cell survival and function. This study investigated effects of the derivatives on beta cell viability and apoptosis, including insulin secretion. Additionally, the study explored if a potential effect was mediated via changes in gene expression linked to beta cell apoptosis pathways . The CGAs, caffeic acid (CA) and ferulic acid (FA), and the CGA metabolites, dihydro ferulic acid (diFA), ferulic acid-4-O- sulphate (FA-4OS) and dihydro caffeic acid-3-O-sulphate (diCA3OS) as well as CFT and TRG were observed. To assess INS-1 beta cell viability, apoptosis and mRNA expression, measurement of cellular ATP content, caspase-3 and -7 activity and quantitative PCR were performed, respectively. Static incubation studies and radioimmunoassays were carried out to measure glucose-stimulated insulin secretion (GSIS) from both INS-1 beta cells and isolated mouse islets. Treatment with selected non-caffeinated coffee derivatives alone and combined significantly enhanced cell viability under basal, non-stressed conditions. These derivatives also directly attenuated cell apoptosis in response to glucolipotoxicity. In addition, a significant decrease in upregulated mRNA levels of Txnip induced by glucolipotoxicity was found in cells treated with all selected CGAs combined with or without CFT+TRG. Upregulated Ddit3 gene expression was also decreased by CFT+TRG. Acute and pre- treatment with diCA-3OS and a cocktail of all coffee compounds enhanced stimulus-induced insulin secretion from INS-1 cells. This enhancement was also observed in cells pre-treated with specific combinations of CGA derivatives with or without CFT+TRG. The GSIS from islets was increased after pre- treatment with CA+FA and the CGA metabolites alone and in combination. However, CFT and TRG, alone and combined, did not modify GSIS in both INS-1 cells and islets.
In conclusion, these findings suggest that a range of non-caffeinated coffee compounds positively modulate beta cell viability and cell apoptosis, which are likely to be mediated via downregulation of Txnip and Ddit3 induced by glucolipotoxicity. In addition, they positively play a role in the regulation of pancreatic beta cell insulin secretion, more specifically, when they are combined. Thus, the decaffeinated coffee compounds exhibit anti-diabetic actions, which have therapeutic potential in the management and prevention of T2D.

Date of Award	11 Apr 2022
Original language	English
Awarding Institution	University of Roehampton
Sponsors	Ede and Ravenscroft Research fund 2018, Roehampton University Sacred Heart Studentship (RUSH) & Sarnsamak’s Family
Supervisor	Adele Costabile (Director of Studies) & Astrid Hauge Evans (Co-Supervisor)