Send Orders for Reprints to reprints@benthamscience.net Current Medicinal Chemistry, 2015, 22, 39-50 39 Procyanidins and Their Healthy Protective Effects Against Type 2 Diabetes Noemí González-Abuín, Montserrat Pinent *,# , Àngela Casanova-Martí, Lluís Arola, Mayte Blay and Anna Ardévol Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain Abstract: This review focuses on the role of procyanidins, the main group of flavonoids, on type 2 diabetes mellitus (T2DM) and insulin resistance. We compile the role of procyanidins on several animal models, and we evaluate their effects on target tissues and analyze the mechanisms involved. Procyanidin treatments in fructose or high-fat induced insulin resistant models were found to improve the damage induced by the diet, thus improving glycemia and insulin sensitivity. The same positive effects were also reported in models of late stage T2DM, in which pancreatic -cells can no longer counteract hyperglycemia. More controversial results were found in genetically obese or cafeteria diet-induced insulin resistant models. Human studies, although limited, fur- ther support the hypoglycemic effect of procyanidins. Regarding their mechanisms, procyanidins have been found to tar- get several tissues involved in glucose homeostasis, which is also discussed in the present review. In insulin-sensitive tis- sues, procyanidins modulate glucose uptake and lipogenesis and improve their oxidative/inflammatory state, the disrup- tion of which is important in T2DM development. In the insulin-producing tissue, the pancreas, procyanidins modulate in- sulin secretion and production and -cell mass, although the available results are divergent. Finally, the gut is another po- tential target for procyanidins. The available data suggest that modulation of the active glucagon-like peptide-1 (GLP-1) levels could partially explain the reported antihyperglycemic effect of these natural compounds. Keywords: -cell, diabetes, glycemia, insulin resistance, procyanidins. # Author’s Profile: Molecular Bioactivity of Food Research Group (MoBioFood). Since 2007 assistant professor at the Univer- sitat Rovira i Virgili (URV), working in the area of nutrigenomics. She has published >40 scientific articles, five reviews and three book chapters. She has supervised three doctoral theses. She has participated in several (>10) projects. 1. PROCYANIDINS, A BRIEF DESCRIPTION This review is centered on the role of the main type of flavonoids, the flavan-3-ols or flavanols, which include the main constitutive molecules of condensed proanthocyanid- ins. Procyanidins, one of the most ubiquitous class of proan- thocyanidins present in nature, are homo-oligomeric proan- thocyanidins with two (3,4) B-ring hydroxyl groups [1]. They are oligomeric structures exclusively formed by po- lymerization of 2 to 10 subunits of the monomeric flavan-3- ols (+)-catechin and (-)-epicatechin [2] (Fig. 1). Procyanidins are found in fruits, bark, leaves, and seeds of many plants and their derived foods such as apples, cocoa, grapes, fruit juices, green tea, chocolate and red wine [1,3]. Daily intake of flavanols and procyanidins within a Western diet was reported to be around 50-100 mg [4], and values in the fifth quintile were estimated to lie in the range of 135- 1,050 mg [5]. Procyanidins have been described as highly bioactive compounds. They have beneficial effects on atherosclerosis and coronary heart diseases, and on different metabolic proc- esses related to the development of these pathologies [6-8]. They have antigenotoxic [9] and cardiovascular protective effects [10,11] and recover inflammatory or oxidative states [12-14]. They also have been suggested as cancer preventive *Address correspondence to this author at the Departament de Bioquímica i Biotecnologia, C. Marcel.li Domingo s/n, 43007 Tarragona, Spain; Tel: 34 977 558778; Fax:34 977558232; E-mail: montserrat.pinent@urv.cat agents due to their antiproliferative effects [15,16]. Moreo- ver, their effects on glucose homeostasis disrupted condi- tions have been investigated; but their exact role on these situations has not been fully resolved (reviewed in [17]). Fig. (1). Structure of procyanidins. Structure of the monomeric flavan-3-ols (+)-Catechin and (-)-Epicatechin, and their oligomers called procyanidins. 1875-533X/15 $58.00+.00 © 2015 Bentham Science Publishers FOR PERSONAL USE