Cooperative Anti-Diabetic Effects of Deoxynojirimycin-Polysaccharide by Inhibiting Glucose Absorption and Modulating Glucose Metabolism in Streptozotocin-Induced Diabetic Mice

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 13C6-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.

A 1H-NMR Based Study on Hemolymph Metabolomics in Eri Silkworm after Oral Administration of 1-Deoxynojirimycin

“…As one additional glycolysis-related product, the augmented lactate levels suggested the enhancement of glycolysis and the decrease of glucose level. This result was also consistent with previous results that DNJ inhibited intestinal glucose absorption and increased the activity of glucose glycolysis enzymes via the relative enhancement in protein expression [ 10 , 39 ]. Moreover, lactate can be used as the energetic substrate in the glycolytic process [ 40 ].…”

Knowledgebase Development and Review for the Function of Omega-3 Polyunsaturated Fatty Acid and Polysaccharide in Diabetes

“…Iancu [57] pointed out that only the diet supplemented with both flaxseed (which was very rich in omega-3 PUFA) and vitamin E resulted in the significant reduction of platelet aggregation and adhesiveness as compared to diabetic animals fed with control diet in diabetic hamsters. You-Gui Li [58] reported that DeoxynojirimycinPolysaccharide Mixture (DPM) decreased blood glucose and reversed the damage to pancreatic β-cells in diabetic mice, thus the anti-hyperglycemic efficacy of this combination was better than that of 1-Deoxynojirimycin (DNJ) or polysaccharide alone. However, whether the combination of omega-3 PUFA and polysaccharides can exert synergistic effects on DM is unknown.…”

Coating rice with mulberry leaves rich in deoxynojirimycin ameliorates hyperglycemia and dyslipidemia in C57BL/KsJdb/dbmice

“…However, hypoglycemic agents are reported to be associated with a risk of lactic acid build-up, and exacerbation of symptoms such as onset of renal failure, hepatotoxicity, and abdominal distension [ 3 ]; in addition, patients with diabetes may develop tolerance to these drugs. Accordingly, research has focused on the identification of bioactive natural compounds that can prevent and suppress diabetes [ 4 5 6 7 8 ]; moreover, natural substances that present in traditional diabetes remedies, or have hypoglycemic effects, have also recently gained attention.…”