甘氨酸保护果糖饮食诱导大鼠糖尿病机制的研究

Glycine protects against type 2 diabetes in rats induced by high fructose diet

目的探讨肠源性内毒素血症(IETM)在果糖饮食诱导的T2DM大鼠中发挥的作用及甘氨酸的保护机制。方法将32只SD大鼠随机分为对照(NC,n=8)组、果糖模型(F,n=8)组、甘氨酸干预(F+G,n=8)组及甘氨酸(G,n=8)组。大鼠自由饮水、进食(标准大鼠饲料),F组给予8%果糖水喂养,F+G组给予8%果糖+1%甘氨酸水喂养。4个月末行OGTT后处死,检测内毒素(LPS)、FPG、TNF-α、IL-6及FIns;计算胰岛素抵抗指数(HOMA-IR)及胰岛β细胞功能指数(HOMA-β);Western blot检测脂肪组织核因子κB(NF-κB)表达。结果 F组出现IETM、IR、OGTT异常及胰岛β细胞功能障碍,FPG、TNF-α、IL-6、FIns、NF-κB表达均高于NC组(P<0.01),F+G组上述指标均有改善(P<0.05)。相关分析显示,血浆LPS与HOMA-IR呈正相关(rs=0.76,P=0.0164)。结论 IETM通过炎症机制参与T2DM发病,甘氨酸减轻IETM,对T2DM有一定的保护作用。

Objective To investigate the roles of intestinal endotoxemia （IETM） in type 2 diabetes （T2DM） rats induced by high fructose-fed diet,and the protective effect of glycine on it.Methods Thirty-two SD rats were randomly divided into normal control（NC,n=8） group,fructose model （F,n=8） group,glycine intervene （F＋G,n=8）group and glycine （G,n=8） group.F group was received 8% fructose,and F＋G group was received 8% fructose and 1% glycine respectively.The rate were sacrificed at month 4.Endotoxin （LPS）,FPG,fasting insulin （FIns） and pro-inflammatory cytokines were measured.HOMA-IR and HOMA-β were calculated.Western blot was used to determine the expression of NF-κB in adipose tissue.Results The levels of LPS,FPG,FIns,pro-inflammatory and HOMA-IR increased （P〈0.01）,HOMA-β was reduced （P〈0.01）,and glucose tolerance was impaired,the expression of NF-κB was significantly up regulated in the F group as compared with the NC group.But the indexes above mentioned in F ＋ G group were partially ameliorated.Conclusion Intestinal endotoxemia contributes to T2DM by inflammatory mechanisms,and glycine has significantly protective effects via alleviating intestinal endotoxemia in T2DM rats.