NMR-based Metabonomics Study of Patients with Cerebral Infraction Complication in Type 2 Diabetes Mellitus

目的应用氢谱核磁共振代谢组学(1H-nMr)方法研究2型糖尿病(T2dM)合并脑梗死患者血清中小分子代谢物代谢轮廓的变化,探讨2型糖尿病合并脑梗死的可能发病机制。方法选择T2dM合并脑梗死患者19例、单纯T2dM患者25例及健康对照者29例,利用1H-nMr方法检测血清的代谢轮廓,通过偏最小二乘判别分析方法,鉴别各组别间血清小分子代谢物的区别。结果从血清偏最小二乘判别分析得分图中可以区分3组患者,与T2dM合并脑梗死有关的特征代谢物包括极低密度脂蛋白、低密度脂蛋白、葡萄糖、乳酸、丙酮酸、3-羟基丁酸、n-乙酰糖蛋白、亮氨酸、缬氨酸、前列腺素d2、前列腺素E2、同型半胱氨酸、氧化三甲胺、甜菜碱等。结论脂类代谢、糖代谢、氨基酸代谢的紊乱可能在T2dM合并脑梗死的发病中起到重要作用。炎症因子、同型半胱氨酸的增加,肠道菌群失调引起的氧化三甲胺、甜菜碱的浓度改变可能也与T2dM合并脑梗死的发生有一定关系。Aim To investigate the possible mechanism of cerebral infarction in type 2 diabetes mellitus(T2DM) through identifying the changes of metabolic products in serum by applying the method of 1H-nuclear magnetic resonance(1H-NMR).Methods Nineteen patients with cerebral infarction complication in T2DM,25 T2DM patients without cerebral infarction and 29 healthy controls were included in our study.The micromolecular substances of each participant in serum were detected by 1H-NMR.The metabolic profile of each participant was obtained.The partial least square discriminant analysis(PLS-DA) was used to examine the difference of metabolic profile among groups.Results Based on the analysis of score plots of groups,the T2DM patients with cerebral infarction,T2DM patients without cerebral infarction and the group of healthy controls were clearly distinguished by applying PLS-DA.The characteristic metabolic products of patients with cerebral infarction complication in T2DM included very low density lipoprotein(VLDL),low density lipoprotein(LDL),glucose,3-hydroxy butanoic acid,lactate,pyruvic acid,glycoprotein,leucine,valine,prostaglandin D2,E2,homocysteine,trimethylamine oxide(TMAO) and betaine.Conclusions The results of our study suggested that the metabolic disorders of lipids,carbohydrate and amino acid may play essential role in the development of T2DM with cerebral infarction.The elevated level of prostaglandin D2,E2 and homocysteine might play a role in the occurrence of cerebral infarction in T2DM.The change of TMAO and betaine which were caused by enteric dysbacteriosis,also might be related to the occurrence of cerebral infarction in type 2 diabetes mellitus

Expression of adiponectin and its receptors in livers of morbidly obese patients with non-alcoholic fatty liver disease

Obesity is one of the risk factors for non-alcoholic fatty liver disease (NAFLD) and a common disease that comprises simple steatosis and non-alcoholic steatohepatitis (NASH), and can eventually lead to liver cirrhosis. Adiponectin is an adipocyte-derived protein that has anti-obesity, antidiabetic and anti-inflammatory properties, and is considered to possess a hepatoprotective function. Its role in the development and progression of NAFLD in morbidly obese patients is unknown. In this study, we examined the expression levels of adiponectin and its receptors in liver biopsies of morbidly obese patients and then determined whether there was an association with the disease severity. Liver biopsies from 30 morbidly obese patients (18 NASH vs 12 steatosis) were analyzed. The needle core biopsies were subjected to routine histological examination and stained immunohistochemically for adiponectin, adiponectin receptor I (adipoRI) and receptor II (adipoRII). The two groups were comparable with respect to body mass index, age and gender distribution. The expression of adiponectin decreased in liver biopsies with NASH as compared to those with simple steatosis (1.61 +/- 0.70 vs 2.25 +/- 0.75, P = 0.028). Spearman's rank correlation coefficient analysis showed that the staining intensity of adiponectin negatively correlated with the grade of inflammation (r = -0.368, P = 0.045) and stage of fibrosis (r = -0.380, P = 0.038). There was no significant difference in expression of adipoRI and adipoRII between the two groups. These findings indicate that decreased liver adiponectin expression may play a role in the development and progression of NAFLD, from simple steatosis to NASH, in morbidly obese patients

A Novel Role of Globular Adiponectin in Treatment with HFD/STZ Induced T2DM Combined with NAFLD Rats

Aims. To evaluate the effects of globular adiponectin (gAd) on treatment of type 2 diabetic rats combined with NAFLD. Materials and Methods. Twenty-one male wistar rats were fed with normal diet ( 7 rats) or high fat diet (HFD) ( 14 rats) for 4 weeks, and then HFD-fed rats were injected with streptozotocin (STZ) to induce type 2 diabetes mellitus (T2DM). Half of T2DM rats were randomly injected with gAd intraperitoneally for 7 days. The expressions of adiponectin receptors (adipoR1/R2) in liver and skeletal muscle tissues were detected through western blotting or RT-qPCR, respectively. Results. Globular adiponectin alleviated the hepatic steatosis and increased insulin secretion. In liver, both the protein and mRNA expressions of adipoR2 in T2DM group decreased (P < 0.05, resp.) in contrast to NC group and increased (P < 0.05 and P < 0.001, resp.) after gAd treatment. But the protein and mRNA expressions of adipoR1 increased (P < 0.05, resp.) in T2DM group and no change was found in the gAd-treated group. In skeletal muscle, the protein and mRNA expressions of adipoR1 and adipoR2 were upregulated in T2DM group and were downregulated after gAd treatment. Conclusions. Globular adiponectin could ameliorate the hepatic steatosis and vary the expressions of adiponectin receptors in liver and skeletal muscle by stimulating insulin secretion