Glucose-lowering effect of Reducose® enriched with 1-deoxyno-jirimycin and L-leucine: Studies on insulin secretion in INS-1 cells and reduction of blood glucose in diabetic rats

Abstract

The extract of mulberry leaf and its active ingredients have already been reported to have antidiabetic effects; however, further studies are required to obtain better quality extracts and higher yields of active ingredients. Reducose (R) is a commercially available aqueous extract of mulberry leaves with a high content of active ingredients. In this study, the biological activities of Reducose (R), 1-deoxynojirimycin, and L-leucine were evaluated using a glucose-stimulated insulin secretion (GSIS) assay. The GSIS assay results were expressed as the glucose-stimulated index (GSI). Considering the pharmacological safety in pancreatic I3-cells, the appropriate non-toxic concentrations were selected by screening for cytotoxicity of Reducose (R), 1-deoxynojirimycin, and L-leucine before the GSIS assay. The effect of Reducose (R), 1-deoxynojirimycin, and Lleucine on glucose-stimulated insulin secretion in INS-1 cells was compared. Reducose (R), 1-deoxynojirimycin, and L-leucine increased the GSI values more effectively than gliclazide (positive control). This was associated with an increase in protein expression, such as peroxisome proliferator-activated receptor-gamma, insulin receptor substrate-2, activated pancreatic and duodenal homeobox-1, which are related to the regulation of pancreatic I3-cell function and survival. In order to elucidate the effect of Reducose (R) in anti-diabetic effects, blood glucose levels, insulin levels, and liver and lipid concentrations were investigated in a Sprague-Dawley rat model of high-fat diet/streptozotocin-induced diabetes. We observed that administration of Reducose (R) can decrease fasting blood glucose levels and reduce the production of AST, ALT, TG, and TC to a similar extent as metformin (positive control). These results suggested that Reducose (R) play a role in promoting GSIS but not enough to show that the content and proportion of 1-deoxynojirimycin and L-leucine play an important role in the GSIS activity of Reducose (R).