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

Li YG, Ji DF, Zhong S, Lv ZQ, Lin TB - PLoS ONE (2013)

Bottom Line: However, the mechanisms behind these effects were not fully understood.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.

View Article: PubMed Central - PubMed

Affiliation: Sericultural Research Institute, Zhejiang Academy of Agricultural Science, Hangzhou, China.

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.

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Related in: MedlinePlus

SGLT1, Na+/k+-ATPase and GLUT2 expression analysis in jejunum.Panel A shows RT-PCR analysis of SGLT1, Na+/k+-ATPase and GLUT2 mRNA expression. Panel B and C show western blot analysis of SGLT1, Na+/k+-ATPase and GLUT2 protein expression in normal, diabetic mice (DM) and diabetic mice treated with DPM (DM+DPM). Density values were normalized to β-actin levels. Data represent mean ±SD from three animals in each group *P<0.05, **P<0.01vs. normal; #P<0.05, ##P<0.01vs. DM.
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pone-0065892-g004: SGLT1, Na+/k+-ATPase and GLUT2 expression analysis in jejunum.Panel A shows RT-PCR analysis of SGLT1, Na+/k+-ATPase and GLUT2 mRNA expression. Panel B and C show western blot analysis of SGLT1, Na+/k+-ATPase and GLUT2 protein expression in normal, diabetic mice (DM) and diabetic mice treated with DPM (DM+DPM). Density values were normalized to β-actin levels. Data represent mean ±SD from three animals in each group *P<0.05, **P<0.01vs. normal; #P<0.05, ##P<0.01vs. DM.

Mentions: To further explore the inhibitory effect of DPM on glucose absorption, we examined the expression of SGLT1, Na+/K+-ATP and GLUT2 in the jejunum by RT-PCR and Western blot. Levels of the mRNA (Fig. 4A) and the corresponding proteins (Fig. 4B, C) of SGLT1, Na+/ K+-ATP and GLUT2 were found to be significantly up-regulated in diabetic mice, which is consistent with previous reports [3], [4], [19]. DPM (150 mg/kg) treatment markedly suppressed expression of these proteins (P<0.01), further supporting our conclusion that DPM can inhibit glucose absorption.


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

Li YG, Ji DF, Zhong S, Lv ZQ, Lin TB - PLoS ONE (2013)

SGLT1, Na+/k+-ATPase and GLUT2 expression analysis in jejunum.Panel A shows RT-PCR analysis of SGLT1, Na+/k+-ATPase and GLUT2 mRNA expression. Panel B and C show western blot analysis of SGLT1, Na+/k+-ATPase and GLUT2 protein expression in normal, diabetic mice (DM) and diabetic mice treated with DPM (DM+DPM). Density values were normalized to β-actin levels. Data represent mean ±SD from three animals in each group *P<0.05, **P<0.01vs. normal; #P<0.05, ##P<0.01vs. DM.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675047&req=5

pone-0065892-g004: SGLT1, Na+/k+-ATPase and GLUT2 expression analysis in jejunum.Panel A shows RT-PCR analysis of SGLT1, Na+/k+-ATPase and GLUT2 mRNA expression. Panel B and C show western blot analysis of SGLT1, Na+/k+-ATPase and GLUT2 protein expression in normal, diabetic mice (DM) and diabetic mice treated with DPM (DM+DPM). Density values were normalized to β-actin levels. Data represent mean ±SD from three animals in each group *P<0.05, **P<0.01vs. normal; #P<0.05, ##P<0.01vs. DM.
Mentions: To further explore the inhibitory effect of DPM on glucose absorption, we examined the expression of SGLT1, Na+/K+-ATP and GLUT2 in the jejunum by RT-PCR and Western blot. Levels of the mRNA (Fig. 4A) and the corresponding proteins (Fig. 4B, C) of SGLT1, Na+/ K+-ATP and GLUT2 were found to be significantly up-regulated in diabetic mice, which is consistent with previous reports [3], [4], [19]. DPM (150 mg/kg) treatment markedly suppressed expression of these proteins (P<0.01), further supporting our conclusion that DPM can inhibit glucose absorption.

Bottom Line: However, the mechanisms behind these effects were not fully understood.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.

View Article: PubMed Central - PubMed

Affiliation: Sericultural Research Institute, Zhejiang Academy of Agricultural Science, Hangzhou, China.

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.

Show MeSH
Related in: MedlinePlus