Cooperative anti-diabetic effects of deoxynojirimycin-polysaccharide by inhibiting glucose absorption and modulating glucose metabolism in streptozotocin-induced diabetic mice

PLoS One. 2013 Jun 6;8(6):e65892. doi: 10.1371/journal.pone.0065892. Print 2013.

Abstract

We had previously shown that deoxynojirimycin-polysaccharide mixture (DPM) not only decreased blood glucose but also reversed the damage to pancreatic β-cells in diabetic mice, and that the anti-hyperglycemic efficacy of this combination was better than that of 1-deoxynojirimycin (DNJ) or polysachharide alone. However, the mechanisms behind these effects were not fully understood. The present study aimed to evaluate the therapeutic effects of DPM on streptozotocin (STZ)-induced diabetic symptoms and their potential mechanisms. Diabetic mice were treated with DPM (150 mg/kg body weight) for 90 days and continued to be fed without DPM for an additional 30 days. Strikingly, decrease of blood glucose levels was observed in all DPM treated diabetic mice, which persisted 30 days after cessation of DPM administration. Significant decrease of glycosylated hemoglobin and hepatic pyruvate concentrations, along with marked increase of serum insulin and hepatic glycogen levels were detected in DPM treated diabetic mice. Results of a labeled (13)C6-glucose uptake assay indicated that DPM can restrain glucose absorption. Additionally, DPM down-regulated the mRNA and protein expression of jejunal Na(+)/glucose cotransporter, Na(+)/K(+)-ATPase and glucose transporter 2, and enhanced the activities as well as mRNA and protein levels of hepatic glycolysis enzymes (glucokinase, phosphofructokinase, private kinase and pyruvate decarboxylas E1). Activity and expression of hepatic gluconeogenesis enzymes (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) were also found to be attenuated in diabetic mice treated with DPM. Purified enzyme activity assays verified that the increased activities of glucose glycolysis enzymes resulted not from their direct activation, but from the relative increase in protein expression. Importantly, our histopathological observations support the results of our biochemical analyses and validate the protective effects of DPM on STZ-induced damage to the pancreas. Thus, DPM has significant potential as a therapeutic agent against diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / therapeutic use*
  • Animals
  • Blood Glucose / drug effects
  • Blotting, Western
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism*
  • Glucose / metabolism
  • Insulin / blood
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Polysaccharides / therapeutic use*
  • Streptozocin / toxicity*

Substances

  • Blood Glucose
  • Insulin
  • Polysaccharides
  • 1-Deoxynojirimycin
  • Streptozocin
  • Glucose

Grant support

This study was supported by the earmarked fund for Modern Agro-industry Technology Research System of China, by Science and Technology Department of Zhejiang Province (2011C22062¼Œ2012C12910), by the Natural Science Foundation of Zhejiang Province (LQ12H31002) and by the Zhejiang Sericultural Sci-Tech Innovation Team (2011R50028). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.