Grape Seed-Derived Procyanidins Have an Antihyperglycemic Effect in Streptozotocin-Induced Diabetic Rats and Insulinomimetic Activity in Insulin-Sensitive Cell Lines

• Published in: Endocrinology (Philadelphia) Vol. 145; no. 11; pp. 4985 - 4990
• Main Authors: Pinent, M, Blay, M, Bladé, M. C, Salvadó, M. J, Arola, L, Ardévol, A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-11-2004; Oxford University Press
• Subjects: 3T3-L1 Cells; Adipocytes; Adipocytes - cytology; Adipocytes - drug effects; Animals; Biflavonoids - pharmacology; Biological and medical sciences; Catechin - pharmacology; Cell lines; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - drug therapy; Diabetes. Impaired glucose tolerance; Disease Models, Animal; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Flavonoids; Fundamental and applied biological sciences. Psychology; Glucose; Glucose - pharmacokinetics; Glucose metabolism; Glucose transporter; Grapes; Hyperglycemia - drug therapy; Hypoglycemic Agents - pharmacology; Insulin; Insulin - metabolism; Kinases; Male; MAP kinase; Medical sciences; Mice; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - drug effects; Myotubes; Oxidative metabolism; Proanthocyanidins - pharmacology; Procyanidins; Rats; Rats, Wistar; Seeds - chemistry; Streptozocin; Translocation; Vertebrates: endocrinology; Vitis - chemistry; Wortmannin; Endocrinopathy; Pancreatic hormone; Vertebrata; Mammalia; Cell line; Rat; Animal; Diabetes mellitus; Rodentia; Insulin; Streptozotocin
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2004-0764

Flavonoids are functional constituents of many fruits and vegetables. Some flavonoids have antidiabetic properties because they improve altered glucose and oxidative metabolisms of diabetic states. Procyanidins are flavonoids with an oligomeric structure, and it has been shown that they can improve the pathological oxidative state of a diabetic situation. To evaluate their effects on glucose metabolism, we administered an extract of grape seed procyanidins (PE) orally to streptozotocin-induced diabetic rats. This had an antihyperglycemic effect, which was significantly increased if PE administration was accompanied by a low insulin dose. The antihyperglycemic effect of PE may be partially due to the insulinomimetic activity of procyanidins on insulin-sensitive cell lines. PE stimulated glucose uptake in L6E9 myotubes and 3T3-L1 adipocytes in a dose-dependent manner. Like insulin action, the effect of PE on glucose uptake was sensitive to wortmannin, an inhibitor of phosphoinositol 3-kinase and to SB203580, an inhibitor of p38 MAPK. PE action also stimulated glucose transporter-4 translocation to the plasma membrane. In summary, procyanidins have insulin-like effects in insulin-sensitive cells that could help to explain their antihyperglycemic effect in vivo. These effects must be added to their antioxidant activity to explain why they can improve diabetic situations.