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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

Effect of DPM (150 mg/kg) on the body weight in STZ-induced diabetic mice.Each point represents the mean ± SD for 10 animals in each group. *P<0.05, **P<0.01vs. Normal.
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pone-0065892-g002: Effect of DPM (150 mg/kg) on the body weight in STZ-induced diabetic mice.Each point represents the mean ± SD for 10 animals in each group. *P<0.05, **P<0.01vs. Normal.

Mentions: In order to identify the therapeutic effects of oral administration of DPM (150 mg/kg) on STZ-induced diabetes, mice were fasted for 12 h before determining their blood glucose levels. As showed in Figure 1, there was a remarkable (P<0.05) elevation in the levels of blood glucose of STZ-induced diabetic mice compared with control animals. Upon treatment with DPM (150 mg/kg) for 90 days, the blood glucose levels of all diabetic mice with different degrees of injury induced by STZ were markedly diminished (29.09±1.24, 24.01±1.82, 17.82±1.57 to 19.38±1.16, 15.29±1.68, 9.75±0.96 mmol/L, respectively). Importantly, the decrease in blood glucose level was not reversed in lower hyperglycemia mice groups (V, VII) after stopping DPM administration for another 30 days (Fig. 1B, C). A slight increase in blood glucose was observed in the more severe hyperglycemia group (III) after stopping DPM administration (Fig. 1A), but did not reach statistical significance compared to the blood glucose levels measured at the 90th day of DPM administration. Additionally, striking decrease of glycosylated hemoglobin (HbA1c) indicated the decrease of glucose concentration in blood, while significantly increased serum insulin indicated that the damaged pancreas had been ameliorated in DPM treated diabetic mice (Table 1). Furthermore, the body weights of normal mice increased throughout the 120 days of observation (Fig. 2). Although slight increase in the body weights of the mice in Group II and Group IV were detected during the experiment, they were still significantly lower compared to the control animals. However, the body weights of mice in Group VI were not markedly different from that of the control group. The body weights of all animals in the DPM treatment groups increased gradually with the passage of time, and no significant difference was observed among these groups compared to the control group. Moreover, no case of diarrhea was found in DPM treated mice throughout the experiment. Taken together, these results indicate that DPM has therapeutic effects against diabetes.


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)

Effect of DPM (150 mg/kg) on the body weight in STZ-induced diabetic mice.Each point represents the mean ± SD for 10 animals in each group. *P<0.05, **P<0.01vs. Normal.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065892-g002: Effect of DPM (150 mg/kg) on the body weight in STZ-induced diabetic mice.Each point represents the mean ± SD for 10 animals in each group. *P<0.05, **P<0.01vs. Normal.
Mentions: In order to identify the therapeutic effects of oral administration of DPM (150 mg/kg) on STZ-induced diabetes, mice were fasted for 12 h before determining their blood glucose levels. As showed in Figure 1, there was a remarkable (P<0.05) elevation in the levels of blood glucose of STZ-induced diabetic mice compared with control animals. Upon treatment with DPM (150 mg/kg) for 90 days, the blood glucose levels of all diabetic mice with different degrees of injury induced by STZ were markedly diminished (29.09±1.24, 24.01±1.82, 17.82±1.57 to 19.38±1.16, 15.29±1.68, 9.75±0.96 mmol/L, respectively). Importantly, the decrease in blood glucose level was not reversed in lower hyperglycemia mice groups (V, VII) after stopping DPM administration for another 30 days (Fig. 1B, C). A slight increase in blood glucose was observed in the more severe hyperglycemia group (III) after stopping DPM administration (Fig. 1A), but did not reach statistical significance compared to the blood glucose levels measured at the 90th day of DPM administration. Additionally, striking decrease of glycosylated hemoglobin (HbA1c) indicated the decrease of glucose concentration in blood, while significantly increased serum insulin indicated that the damaged pancreas had been ameliorated in DPM treated diabetic mice (Table 1). Furthermore, the body weights of normal mice increased throughout the 120 days of observation (Fig. 2). Although slight increase in the body weights of the mice in Group II and Group IV were detected during the experiment, they were still significantly lower compared to the control animals. However, the body weights of mice in Group VI were not markedly different from that of the control group. The body weights of all animals in the DPM treatment groups increased gradually with the passage of time, and no significant difference was observed among these groups compared to the control group. Moreover, no case of diarrhea was found in DPM treated mice throughout the experiment. Taken together, these results indicate that DPM has therapeutic effects against diabetes.

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