Effect of long-term supplementation of low molecular weight chitosan oligosaccharide (GO2KA1) on fasting blood glucose and HbA1c in db/db mice model and elucidation of mechanism of action.

Effect of long-term supplementation of low molecular weight chitosan oligosaccharide (GO2KA1) on fasting blood glucose and HbA1c in db/db mice model and elucidation of mechanism of action.
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DOI:
10.1186/1472-6882-14-272
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发表时间:
2014-07-29
影响因子:
--
通讯作者:
Kwon YI
Kwon YI
中科院分区:
医学3区
文献类型:
--
作者:
Kim JG;Jo SH;Ha KS;Kim SC;Kim YC;Apostolidis E;Kwon YI

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2型糖尿病是发达国家的一个严重问题。使用天然产品预防前驱糖尿病发展为2型糖尿病似乎是一种具有成本效益的解决方案。以前,我们表明,酶消化的低分子量壳寡糖与分子量(MW)低于1,000 Da(GO2 KA 1)有潜力的高血糖症的管理。在这项研究中,我们使用db/db小鼠模型评估了长期补充GO2 KA 1对高血糖症的影响。此外,我们使用相同的db/db小鼠模型评估了GO2 KA 1对蔗糖酶和葡糖淀粉酶活性和表达的影响。42天后,我们观察到GO2 KA 1补充剂以与已知的抗糖尿病药物阿卡波糖相似的方式降低血糖水平和HbA 1c。当使用酶测定法评估GO2 KA 1和对照小鼠的蔗糖酶和葡糖淀粉酶活性时,我们观察到GO2 KA 1显著抑制肠的所有3个部分中的蔗糖酶,而葡糖淀粉酶活性仅在中下部显著降低。当评估蔗糖酶-异麦芽糖酶(SI)复合物在mRNA水平上的表达时,我们观察到GO2 KA 1在上部具有最小的抑制作用,在中部具有更显著的抑制作用,而在下部观察到最高的抑制作用。我们的研究结果表明,长期补充GO2 KA 1在db/db小鼠的结果显着降低血糖和HbA 1c,与阿卡波糖的水平相似。此外,我们的研究结果证实了以前的体外观察,即GO2 KA 1对碳水化合物水解酶,即蔗糖酶,麦芽糖酶和SI复合物具有抑制作用。这项研究的结果为使用GO2 KA 1通过抑制碳水化合物水解酶来预防2型糖尿病提供了强有力的理论基础。根据该动物试验的结果,将设计并开展临床试验。
Type 2 diabetes is a serious problem for developed countries. Prevention of prediabetes progression to type 2 diabetes with the use of natural products appears to a cost-effective solution. Previously we showed that enzymatically digested low molecular weight chitosan-oligosaccharide with molecular weight (MW) below 1,000 Da (GO2KA1) has potential for hyperglycemia management. In this study we evaluated the effect of long-term supplementation of GO2KA1 on hyperglycemia using a db/db mice model. Additionally, we evaluated the effect of GO2KA1 on sucrase and glucoamylase activities and expression, using the same db/db mice model. After 42 days we observed that GO2KA1 supplementation reduced both the blood glucose level and HbA1c in a similar manner with a known anti-diabetic drug, acarbose. When the sucrase and glucoamylase activities of GO2KA1 and control mice were evaluated using enzymatic assay, we observed that GO2KA1 significantly inhibited sucrase in all 3 parts of the intestine, while glucoamylase activity was significantly reduced only in the middle and lower part. When the sucrase-isomaltase (SI) complex expression on mRNA level was evaluated, we observed that GO2KA1 had minimal inhibitory effect on the upper part, more pronounced inhibitory effect on the middle part, while the highest inhibition was observed on the lower part. Our findings suggest that long-term GO2KA1 supplementation in db/db mice results to significant blood glucose and HbA1c reduction, to levels similar with those of acarbose. Furthermore, our findings confirm previous in vitro observations that GO2KA1 has inhibitory effect on carbohydrate hydrolysis enzymes, namely sucrase, maltase and SI complex. Results from this study provide a strong rationale for the use of GO2KA1 for type 2 diabetes prevention, via inhibition of carbohydrate hydrolysis enzymes. Based on the findings of this animal trial, clinical trials will be designed and pursued.
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