Chlorogenic Acid Stimulates Glucose Transport in Skeletal Muscle via AMPK Activation: A Contributor to the Beneficial Effects of Coffee on Diabetes

Abstract

Chlorogenic acid (CGA) has been shown to delay intestinal glucose absorption and inhibit gluconeogenesis. Our aim was to investigate the role of CGA in the regulation of glucose transport in skeletal muscle isolated from db/db mice and L6 skeletal muscle cells. Oral glucose tolerance test was performed on db/db mice treated with CGA and soleus muscle was isolated for 2-deoxyglucose transport study. 2DG transport was also examined in L6 myotubes with or without inhibitors such as wortmannin or compound c. AMPK was knocked down with AMPKα1/2 siRNA to study its effect on CGA-stimulated glucose transport. GLUT 4 translocation, phosphorylation of AMPK and Akt, AMPK activity, and association of IRS-1 and PI3K were investigated in the presence of CGA. In db/db mice, a significant decrease in fasting blood sugar was observed 10 minutes after the intraperitoneal administration of 250 mg/kg CGA and the effect persisted for another 30 minutes after the glucose challenge. Besides, CGA stimulated and enhanced both basal and insulin-mediated 2DG transports in soleus muscle. In L6 myotubes, CGA caused a dose- and time-dependent increase in glucose transport. Compound c and AMPKα1/2 siRNA abrogated the CGA-stimulated glucose transport. Consistent with these results, CGA was found to phosphorylate AMPK and ACC, consistent with the result of increased AMPK activities. CGA did not appear to enhance association of IRS-1 with p85. However, we observed activation of Akt by CGA. These parallel activations in turn increased translocation of GLUT 4 to plasma membrane. At 2 mmol/l, CGA did not cause any significant changes in viability or proliferation of L6 myotubes. Our data demonstrated for the first time that CGA stimulates glucose transport in skeletal muscle via the activation of AMPK. It appears that CGA may contribute to the beneficial effects of coffee on Type 2 diabetes mellitus.

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Light-Roasted Green Coffee Extract Improved Adiponectin, Insulin Resistance, and Metabolic Profile of Metabolic Syndrome Rat Model

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“…Phenolic acid conjugates are recognized as antioxidants and have anti-inflammatory properties demonstrated in vitro and in vivo (dos Santos et al, 2006: Prior, 2003Sato et al, 2011). Studies have also reported hypotensive, anti-carcogenic and anti-diabetic effects for these compounds (Ong et al, 2012;Suzuki et al, 2006;Yang et al, 2012) Polyphenol oxidase mediated browning of cut eggplant fruit surfaces due to oxidation of phenolic compounds poses a seeming contradiction for development of eggplant cultivars with improved culinary quality and nutritive value. However, Prohens et al (2007) reported wide variation for browning of cut eggplant fruit surfaces and total phenolics content with only 15% -23% of the total variation for browning attributed to phenolics content.…”