Whole Grain Brown Rice Extrudate Ameliorates the Symptoms of Diabetes by Activating the IRS1/PI3K/AKT Insulin Pathway in db/db Mice

The therapeutic benefits of whole grains on diabetes mellitus have been continuously confirmed by in-depth research. To date, limited studies have investigated the effect of extruded products of whole grains on the insulin signaling pathway in vivo. This study investigated the effects of oral consumption of whole grain extrudate, including 97% brown rice and 3% defatted rice bran (w/w, BRD), on glucose metabolism and the hepatic insulin signaling pathway in C57BL/KsJ-db/db mice. BRD treatment induced a remarkable reduction in blood glucose. Moreover, glucose intolerance and insulin resistance were ameliorated in the BRD-treated group compared with those in the db/db control group. BRD also increased the hepatic glycogen content by reducing the expression and increasing the phosphorylation of glycogen synthase kinase 3β (GSK3β). The activities of glucose-6-phosphatase and phosphoenolpyruvate carboxylase and their respective mRNA expression levels in the liver were simultaneously decreased in the BRD-treated group. BRD also significantly upregulated the expression of phosphatidylinositol 3-kinase (PI3K) and increased the phosphorylation of insulin receptor substrate 1 (IRS1) and protein kinase B (AKT). These results indicate that BRD exhibits antidiabetic potential by activating the IRS1/PI3K/AKT signaling pathway, further regulating the expression of the FOXO1 gene and p-GSK3β protein, thus inhibiting hepatic gluconeogenesis, increasing hepatic glycogen storage, and improving insulin resistance. Therefore, BRD could be used as a functional ingredient to alleviate the symptoms of hyperglycemia.