Procyanidin Promotes Translocation of Glucose Transporter 4 in Muscle of Mice through Activation of Insulin and AMPK Signaling Pathways

Abstract

Procyanidins are the oligomeric or polymeric forms of epicatechin and catechin. In this study, we isolated and purified dimer to tetramer procyanidins from black soybean seed coat and investigated the anti-hyperglycemic effects by focusing on glucose transporter 4 (GLUT4) translocation and the underlying molecular mechanism in skeletal muscle of mice. The anti-hyperglycemic effects of procyanidins were also compared with those of monomer (−)-epicatechin (EC) and major anthocyanin, cyanidin-3-O-β-glucoside (C3G). To investigate GLUT4 translocation and its related signaling pathways, ICR mice were orally given procyanidins, EC and C3G in water at 10 μg/kg body weight. The mice were sacrificed 60 min after the dose of polyphenols, and soleus muscle was extracted from the hind legs. The results showed that trimeric and tetrameric procyanidins activated both insulin- and AMPK-signaling pathways to induce GLUT4 translocation in muscle of ICR mice. We confirmed that procyanidins suppressed acute hyperglycemia with an oral glucose tolerance test in a dose-dependent manner. Of these beneficial effects, cinnamtannin A2, one of the tetramers, was the most effective. In conclusion, procyanidins, especially cinnamtannin A2, significantly ameliorate postprandial hyperglycemia at least in part by promoting GLUT4 translocation to the plasma membrane by activating both insulin- and AMPK-signaling pathways.

Influence of Saskatoon Berry and Cyanidin-3-Glucoside on Gut Microbiota and Relationship with Metabolism and Inflammation in High Fat-High Sucrose Diet-Induced Insulin Resistant Mice

“…The results of the present study demonstrated that C3G induced similar hypoglycemic and hypolipidemic effects as SBp containing comparable amount of C3G in HFHS diet-induced insulin resistant mice. The ndings of the present study are consistent with the previous studies on the effects of Saskatoon berry and C3G in glucose and lipid metabolism reported by our and other groups [11,20,23].…”

“…Previous studies demonstrated that C3G increased the translocation of glucose transporter-4 in skeletal muscle through the activation of insulin and AMP protein kinase pathway in mice [20]. C3G also augmented glucose-induced insulin secretion in INS-1E pancreatic β-cells and glucose uptake in HepG2 hepatocytes [21].…”

Japanese quince (Chaenomeles japonica L.) fruit polyphenolic extract modulates carbohydrate metabolism in HepG2 cells via AMP-activated protein kinase

“…Phenolic compounds influence on hepatic GLUT4 level and/or activity has been so far scarcely evaluated, but recently Doan et al reported results of in vivo studies, where elevated hepatic GLUT4 mRNA levels were observed after the treatment of mice with gallic acid (2015). Independently, Ashida's team observed GLUT4 translocation after treatment of mice with dimer to tetramer procyanidins from black soybean seed coat and this effect was accompanied by AMPK activation (Yamashita et al, 2016). Other studies proved that the EGCG activation of AMPK was mediated by the Ca 2+ /calmodulin-dependent protein kinase kinase (CaMKK) dependent on ROS production (Collins et al, 2007).…”

“…Taking into account that these fruits are a rich source of polyphenolic compounds (mainly catechins and procyanidin oligomers) possessing numerous biological activities (Strugała et al, 2016;Tarko et al, 2014;Bahadoran et al, 2013;Lewandowska et al, 2013;Gorlach et al, 2011;Stręk et al, 2007), we hypothesized that JQ extract can also activate AMPK. Recent reports evidenced black soybean seed coat and grape seed procyanidins as the agents responsible for AMPK activation and glucose uptake in mice and rats (Yamashita et al, 2016;Crescenti et al, 2015;Kurimoto et al, 2013). However, to the best of our knowledge, there are no earlier reports on Japanese quince polyphenols influencing glucose metabolism, thus the aim of the study was to test JQ effect on the AMPK activation.…”

In Vitro Antidiabetic Activity Affecting Glucose Uptake in HepG2 Cells Following Their Exposure to Extracts of Lauridia tetragona (L.f.) R.H. Archer

“…Studies using extracts from plants have shown potential in improving diabetes following a significant improvement in glucose uptake [5][6][7][8][9]. Most of these plants have been reported to contain polyphenols as one of their active principles and recent reports also suggest the antidiabetic property of phenolics compounds [10,11]. α-glucosidase is the enzyme that catalyzes the key step of carbohydrate digestion and glucose release.…”