(-)-Epicatechin in the Control of Glucose Homeostasis: Involvement of Redox-regulated Mechanisms

Emerging evidence supports a beneficial action of the flavan-3-ol (-)-epicatechin (EC) on insulin sensitivity and potential impact on the development/progression of type 2 diabetes (T2D). In humans, supplementation with EC-rich foods, extracts, and pure EC improves insulin sensitivity and glucose tolerance in normal weight, overweight, obese and T2D individuals. These effects of EC are also observed in rodent models of diet-induced obesity and T2D. The events involved in the development of insulin resistance and T2D are multiple and interrelated. EC has been shown to inhibit inflammation, oxidative and endoplasmic reticulum stress, to modulate mitochondrial biogenesis and function, and to regulate events in the gastrointestinal tract and the pancreas that impact glucose homeostasis. A downregulation of oxidant production, particularly through direct inhibition or suppression of NADPH oxidase expression, and of redox sensitive signals (NF-κB, JNK1/2) that inhibit the insulin pathway, appear to be central to the beneficial actions of EC on insulin sensitivity. Overall, EC seems to have a positive role in the regulation of glucose homeostasis, however definitive answers on its importance for the management of T2D will depend on further clinical and mechanistic studies.