Trypsin-Treated beta-Lactoglobulin Improves Glucose Tolerance in C57BL/6 Mice by Enhancing AMPK Activation and Glucose Uptake in Hepatocytes

摘要

It was reported that trypsin-treated beta-lactoglobulin (beta-LG) had a glucose-lowering effect in the oral glucose tolerance test (OGTT) in mice and a dipeptidyl peptidase-4 (DPP-4) inhibition activity in vitro. However, whether trypsin-treated beta-LG improves glucose tolerance by inhibiting DPP-4 in vivo has not yet been examined, and the mechanism of the glucose-lowering effect of trypsin-treated beta-LG is thus unclear. Here we investigated the detailed mechanism underlying the glucose tolerance effect of trypsin-treated beta-LG. The oral administration of trypsin-treated beta-LG significantly decreased the blood glucose concentrations in both the OGTT and an intraperitoneal glucose tolerance test (IPGTT). However, trypsin-treated beta-LG did not increase the insulin secretion after glucose loading. Trypsin-treated beta-LG potently increased the level of phosphorylated AMP-activated protein kinase (AMPK) in human hepatocellular carcinoma (HepG2) cells and in mice hepatocytes. Moreover, trypsin-treated beta-LG significantly enhanced glucose uptake into the HepG2 cells. These results indicate that trypsin-treated beta-LG decreases blood glucose levels after glucose loading by upregulating AMPK activation and glucose uptake in the liver, which could contribute to the reduction of postprandial hyperglycemia.