Exploration of Hypoglycemic Activity of Extract and Evaluation of the Molecular Mechanisms.

Although the hypoglycemic potential of brewer's yeast extract has been reported, there is limited information pertaining to the hypoglycemic ingredients of extract and their mechanisms of action available. This study aimed to investigate the in vivo and in vitro hypoglycemic effect of extract and to elucidate its molecular mechanisms. extract was mainly composed of proteins followed by carbohydrates. In diabetic rats, oral administration of extract significantly reduced the levels of plasma glucose and enhanced the activity of hepatic glucose-6-phosphatase dehydrogenase. Treatment with extract increased the localization of type 4 glucose transporter (GLUT4), PTP, and insulin receptor at 3T3-L1 cell membranes and raised the levels of P38 MAPK, PI3K, and AKT in the cytosol. In agreement with these results, pretreatment of 3T3-L1 cells with inhibitors of PTP, PI3K, Akt/PKB, and p38 MAPK inhibited glucose uptake induced by application of extract. Most importantly, a 54 kDa protein with hypoglycemic activity was identified and suggested as the major ingredient contributing to the hypoglycemic activity of extract. In summary, these results clearly confirm the hypoglycemic activity of extract and provide critical insights into the underlying molecular mechanisms.