1-deoxynojirimycin inhibits glucose absorption and accelerates glucose metabolism in streptozotocin-induced diabetic mice

Abstract

We investigated the role of 1-deoxynojirimycin (DNJ) on glucose absorption and metabolism in normal and diabetic mice. Oral and intravenous glucose tolerance tests and labeled 13C6-glucose uptake assays suggested that DNJ inhibited intestinal glucose absorption in intestine. We also showed that DNJ down-regulated intestinal SGLT1, Na+/K+-ATP and GLUT2 mRNA and protein expression. Pretreatment with DNJ (50 mg/kg) increased the activity, mRNA and protein levels of hepatic glycolysis enzymes (GK, PFK, PK, PDE1) and decreased the expression of gluconeogenesis enzymes (PEPCK, G-6-Pase). Assays of protein expression in hepatic cells and in vitro tests with purified enzymes indicated that the increased activity of glucose glycolysis enzymes was resulted from the relative increase in protein expression, rather than from direct enzyme activation. These results suggest that DNJ inhibits intestinal glucose absorption and accelerates hepatic glucose metabolism by directly regulating the expression of proteins involved in glucose transport systems, glycolysis and gluconeogenesis enzymes.

A Comparison of Food-grade Folium mori Extract and 1-Deoxynojirimycin for Glycemic Control and Renal Function in Streptozotocin-induced Diabetic Rats

“…However, 1-DNJ has been demonstrated to improve the glycemic control in alloxan-induced diabetic mice at doses of 50 and 100 mg/kg and in STZ-induced diabetic rats at a dose of 50 mg/kg. [1119] The present study demonstrated the effectiveness of 1-DNJ as an anti-diabetic agent at a dose of 30 mg/kg, which is lower than what has been previously reported. Another novel finding of the present study is that despite the fact that 1-DNJ lowered fasting blood glucose to a greater extent than the same dose of FM, the latter improved body weight and skeletal muscle weight to a greater extent than the former, suggesting an overall beneficial effect of FM on energy metabolism.…”

Nutritional and functional components of mulberry leaves from different varieties: Evaluation of their potential as food materials

“…It showed high αglucosidase inhibitory, thereby suppressed postprandial blood glucose and prevented diabetes mellitus and decreased lipid accumulation. [32][33][34] Our results ( Table 1) showed that there were significantly differences on the DNJ content in mulberry leaves from the selected varieties (P < 0.05). The DNJ content varied from 0.08 to 1.12 mg/g DW.…”

Physiological Effects and Organ Distribution of <i>Bacillus amyloliquefaciens</i> AS385 Culture Broth Powder Containing 1-Deoxynojirimycin in C57BL/6J Mice

“…a-Glucosidase inhibitors block the activity of a-glucosidase in the small intestine, thus limit the conversion rate of oligosaccharides and disaccharides into monosaccharides, which necessary for absorption into the bloodstream (37). DNJ is as a potent inhibitor of a-glucosidase (1-3) and has demonstrated anti-hyperglycemic effect by delaying intestinal glucose absorption and accelerating hepatic glucose metabolism in study using streptozotocin-induced diabetic mice (38,39). In the previous study, we found that single oral administration of DNJ-enriched mulberry leaves powder significantly suppressed the elevation of postprandial blood glucose in human (3).…”