Plant polyphenols mechanisms of action on insulin resistance and against the loss of pancreatic beta cells

Diabetes mellitus describes a group of metabolic disorders characterized by a prolonged period hyperglycemia with long-lasting detrimental effects on the cardiovascular and nervous systems, kidney, vision, and immunity. Many plant polyphenols are shown to have beneficial activity for the prevention and treatment of diabetes, by different mechanisms. This review article is focused on synthesizing the mechanisms by which polyphenols decrease insulin resistance and inhibit loss of pancreatic islet β-cell mass and function. To achieve the objectives, this review summarizes the results of the researches realized in recent years in clinical trials and in various experimental models, on the effects of foods rich in polyphenols, polyphenolic extracts, and commercially polyphenols on insulin resistance and β-cells death. Dietary polyphenols are able to reduce insulin resistance alleviating the IRS-1/PI3-k/Akt signaling pathway, and to reduce the loss of pancreatic islet β-cell mass and function by several molecular mechanisms, such as protection of the surviving machinery of cells against the oxidative insult; increasing insulin secretion in pancreatic β-cells through activation of the FFAR1; cytoprotective effect on β-cells by activation of autophagy; protection of β-cells to act as activators for anti-apoptotic pathways and inhibitors for apoptotic pathway; stimulating of insulin release, presumably by transient ATP-sensitive K⁺ channel inhibition and whole-cell Ca²⁺ stimulation; involvement in insulin release that act on ionic currents and membrane potential as inhibitor of delayed-rectifier K⁺ current (I_K(DR)) and activator of current. dietary polyphenols could be used as potential anti-diabetic agents to prevent and alleviate diabetes and its complications, but further studies are needed.