Flavonoids are polyphenolic compounds that are abundant in fruits and vegetables, and increasing evidence demonstrates a positive relationship between consumption of flavonoid-rich foods and disease prevention. Epidemiological, in vitro and animal studies support the beneficial effects of dietary flavonoids on glucose and lipid homeostasis. It is encouraging that the beneficial effects of some flavonoids are at physiological concentrations and comparable to clinically-used anti-diabetic drugs; however, clinical research in this field and studies on the anti-diabetic effects of flavonoid metabolites are limited. Flavonoids act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, hepatocytes, adipocytes and skeletal myofibers. Flavonoids may exert beneficial effects in diabetes by (i) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (ii) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (iii) reducing insulin resistance, inflammation and oxidative stress in muscle and fat and (iv) increasing glucose uptake in skeletal muscle and white adipose tissue. This review highlights recent findings on the anti-diabetic effects of dietary flavonoids, including flavan-3-ols, flavanones, flavonols, anthocyanidins, flavones and isoflavones, with particular emphasis on the studies that investigated the cellular and molecular mechanisms involved in the beneficial effects of the compounds.
Keywords: ACC; AMPK; ATP; Acetyl Co-A carboxylase; Adenosine monophosphate-activated protein kinase; Adenosine triphosphate; BBE; BFE; Bayberry fruit extract; Bilberry extract; Carnitine palmitoyltransferase I; DM; Diabetes; Diabetes mellitus; ECG; EGC; EGCG; ER; Endoplasmic reticulum; Epicatechin gallate; Epigallocatechin; Epigallocatechin gallate; FFA; Flavonoids; FoXO1; Forkhead box protein O1; Free fatty acid; G6Pase; GK; GLUT; GSIS; Glucokinase; Glucose transporter; Glucose-6-phosphatase; Glucose-stimulated insulin secretion; HSP; Heat shock proteins; Hyperglycemia; IR; IRS; Insulin receptor; Insulin receptor substrate; Intraperitoneal; Islets; JNK; L-Cpt-1; MAPK; Mitogen activated protein kinase; NF-κB; NOD; Non-obese diabetic mice; Nuclear factor-κB; PDX-1; PEPCK; PGC-1α; PKC; PPAR; Pancreatic duodenal homeobox-1; Pancreatic β-cells; Peroxisome proliferator-activated receptor gamma coactivator-1-α; Phosphoenolpyruvate carboxykinase; Polyphenols; Protein kinase C; RBP4; RIN cells; ROS; Rat insulinoma cells; Reactive oxygen species; Retinol binding protein-4; STZ; Streptozotocin; T1D; T2D; TNFα; TZD; Thiazolidinedione; Tumor necrosis factor α; Type 1 diabetes mellitus; Type 2 diabetes mellitus; WAT; White adipose tissue; c-jun amino terminal kinase; cAMP; cyclic adenosine mono phosphate; i.p.; peroxisome proliferator activated receptor.