Obesity and diabetes are major health problems in much of the world, and extensive work is being done to improve glucose control in these individuals.  Glucagon-like peptide-1 (GLP-1) is a target for this intervention through the use of several pharmaceutical agonists.  Work is also being done to identify diet-derived molecules that may also impact signaling through GLP-1 in order to improve glucose regulation.  Flavanols, like (-)-epicatechin (EC) and anthocyanins (AC), have demonstrated improvements in cardiometabolic health biomarkers, including glucose metabolism.  However, their ability to influence GLP-1 is not completely understood, so Cremonini and colleagues conducted work to further define their potential impacts and their work is published in the June 2021 issue of The Journal of Nutrition.

The experiments were conducted using 6 week old mice or GLUTag cells, which are enteroendocrine cells capable of expressing the glucagon gene and secrete GLP-1.  The mice received a control diet or one supplemented with either 40 mg AC/kg body weight or 20 mg EC/kg body weight for 14 or 15 weeks, respectively.  The expression of preproglucagon (Gcg) and the enzyme that cleaves GLP-1, dipeptidyl peptidase IV (Dpp-iv) were determined in intestinal tissues.  GLUTag cells were incubated with AC, protocatechuic acid, EC or a control media.  Secretion of GLP-1 and the pathways involved in its release were determined.

Plasma concentrations of GLP-1 and Gcg mRNA in the ileum and colon were increased by both EC and AC.  The mRNA levels of Dpp-iv were lower in the ileum of mice consuming AC, whereas activity of DPP-IV was decreased in the plasma of mice consuming EC.  In vitro GLP-1 secretion, cyclin adenosine monophosphate levels and activated protein kinase A levels were increased by cyanidin, delphinidin, protocatechuic acid, and EC.  Observations from these studies led the authors to conclude that AC and EC regulate different steps in the GLP-1 pathways and that the cyanidin, delphinidin, protocatechuic acid and EC stimulate GLP-1 secretion by activating the PKA-dependent pathway.  Furthermore, they suggest that consumption of these flavonoids help to sustain intestinal and glucose homeostasis through their impacts on GLP-1 metabolism.

Heiss and Rodriguez-Mateos state the work of Cremonini and colleagues provide compelling evidence in support of the effect of flavonoids on glucose metabolism by influencing GLP-1 metabolism.  They recommend that caution should be used in extrapolating the responses to those in humans as the amounts used were high, compared to normal human dietary patterns.  They also raise a question concerning the levels and specific metabolites of the tested molecules, as polyphenol metabolism in rodents and humans vary considerably.  They conclude by suggesting the evidence provided supports the need for human studies to verify the impact of these dietary bioactives on glucose regulation.


Cremonini E, Daveri E, Mastaloudis A, Oteiza PI.  (-)-Epicatechin and anthocyanins modulate GLP-1 metabolism:  Evidence from C57BL/6J mice and GLUTag cells. The Journal of Nutrition, Volume 151, Issue 6, June 2021, Pages 1497–1506, https://doi.org/10.1093/jn/nxab029.

Heiss C, Rodriguez-Mateos A. Experimental evidence that (-)-epicatechin and anthocyanins modulate glucagon-like peptide-1 metabolism:  Relevant for humans? The Journal of Nutrition, Volume 151, Issue 6, June 2021, Pages 1365–1366, https://doi.org/10.1093/jn/nxab081.

Images via canva.com.