The Coffee Connection: Anti-Diabetic Potential of Coffee-Derived Compounds and their Underlying Cellular and Microbial Mechanisms

Type II Diabetes (T2D) is characterized by chronically elevated fasting blood glucose resulting from insulin resistance. Epidemiologically, there is an inverse relationship between habitual coffee consumption and risk of T2D (1-3). While this relationship warrants further study, compounds naturally occurring in coffee may possess anti-diabetic potential. Matairesinol (MA), a coffee-derived polyphenol, has been shown to be effective in mitigating weight gain and fat mass accrual which are associated with T2D (4). Enterolactone (ENL), the metabolite of MA, has demonstrated the ability to act on L6 myotubes increasing basal glucose uptake while hindering triacylglycerol uptake in HEPA1-6 cells as well as adipogenesis in 3T3-L1 fat cells (4). Our lab recently found that MA and ENL promote glucose uptake in 3T3-L1 adipocytes. Further elucidation of the pathway by which ML and ENL increase glucose uptake reveals valuable insights that may guide future research about glucose uptake and metabolic syndrome. Coffee consumption may also be alleviating T2D through gut microbiome modulation. Dysbiosis of the gut microbiome, which is associated with T2D, can involve an increased ratio of Firmicutes: Bacteroidetes (5). We found that MA had a bacteriostatic effect on Enterococcus faecalis, a member of the Firmicutes phylum, while promoting the growth of Bacteroides fragilis, a member of the Bacteroidetes phylum. Ultimately, our lab seeks to characterize the mechanisms by which select coffee-derived compounds promote glucose uptake in 3T3-L1 adipocytes and determine the effects of these compounds on the growth of metabolic syndrome-associated gut microflora. We will attempt to draw connections between the impact of these and other coffee-derived compounds on metabolism at a microbial and cellular level. This research may reveal the potentially holistic benefits of these compounds as potential chemotherapeutic agents to promote improvements in therapies for T2D. 1. M. Carlström, S. C. Larsson, Coffee consumption and reduced risk of developing type 2 diabetes: a systematic review with meta-analysis. Nutrition Reviews. 76, 395–417 (2018). 2. H. Kolb, S. Martin, K. Kempf, Coffee and Lower Risk of Type 2 Diabetes: Arguments for a Causal Relationship. Nutrients. 13, 1144 (2021). 3. R. M. van Dam, F. B. Hu, W. C. Willett, Coffee, Caffeine, and Health. The New England Journal of Medicine. 383, 369–378 (2020). 4. Carmichael, R.E., K.A. Wilkinson, and T.J. Craig. 2019. Insulin-dependent GLUT4 trafficking is not regulated by protein SUMOylation in L6 myocytes. Scientific Reports. 9:6477. doi: 10.1038/s41598-019-42574-3. 5. Bielka W, Przezak A, Pawlik A. The Role of the Gut Microbiota in the Pathogenesis of Diabetes. Int J Mol Sci. 2022 Jan 1;23(1):480.