Abnormal magnesium metabolism in etiology of salt-sensitive hypertension and type 2 diabetes mellitus

A previously unknown genetic defect in magnesium metabolism (i.e., the magnesium-binding defect [MgBD]) was found to be associated with the cause of “salt-sensitive” essential hypertension in humans and rats. It inhibits the entrance of Mg²⁺ into the cell so that the intracellular concentrations of Mg²⁺ and MgATP²⁻ are decreased. Consequently, the 300 enzyme reactions in the cell, especially the 100 that either use or produce MgATP²⁻, are inhibited. Thus, because the extrusion of intracellular Na⁺ requires MgATP²⁻, hypertension results when the involved MgATP²⁻ requiring enzyme is inhibited. The MgBD is corrected by the tachykinin substance P, which occurs in normal blood plasma, and by the pentapeptide and its contained tetrapeptide, which are released from the C-terminal region of substance P by plasma aminopeptidases. In vivo, the intravenous administration of the tetrapeptide corrects the hypertension and the MgBD as well. The MgBD also occurs in type 2 diabetes mellitus and, thus, the decreased intracellular concentrations of Mg²⁺ and MgATP²⁻ ions appear to be involved also in the cause of this disease, which is reputed to be the fifth most deadly disease in the world.     

A Soluble Activin Receptor Type IIB Does Not Improve Blood Glucose in Streptozotocin-Treated Mice

Type 1 diabetes mellitus (T1DM), or insulin dependent DM, is accompanied by decreased muscle mass. The growth factor myostatin (MSTN) is a negative regulator of muscle growth, and a loss of MSTN signaling has been shown to increase muscle mass and prevent the development of obesity, insulin resistance and lipodystrophic diabetes in mice. The effects of MSTN inhibition in a T1DM model on muscle mass and blood glucose are unknown. We asked whether MSTN inhibition would increase muscle mass and decrease hyperglycemia in mice treated with streptozotocin (STZ) to destroy pancreatic beta cells. After diabetes developed, mice were treated with a soluble MSTN/activin receptor fused to Fc (ACVR2B:Fc). ACVR2B:Fc increased body weight and muscle mass compared to vehicle treated mice. Unexpectedly, ACVR2B:Fc reproducibly exacerbated hyperglycemia within approximately one week of administration. ACVR2B:Fc treatment also elevated serum levels of the glucocorticoid corticosterone. These results suggest that although MSTN/activin inhibitors increased muscle mass, they may be counterproductive in improving health in patients with T1DM.     

Reduction in Incidence of Diabetes,Hypertension and Lipid Disturbances after Intentional Weight Loss Induced by Bariatric Surgery: the SOS Intervention Study

SJÖSTRÖM, c. DAVID, LAUREN LISSNER, HANS WEDEL, and LARS SJÖSTRÖM. Reduction in incidence of diabetes, hypertension and lipid disturbances after intentional weight loss induced by bariatric surgery: the SOS Intervention Study. Obes Res. Objective: To examine the effect of a large, long standing and intentional weight reduction on the incidence of diabetes, hypertension and lipid disturbances in severely obese individuals as compared to weight-stable obese controls. Research Methods and Procedures: The ongoing prospective SOS (Swedish Obese Subjects) intervention consists of a surgically treated group and a matched control group obtaining conventional obesity treatment. This report is based on 845 surgically treated patients and 845 controls (BMI41. 0±4. 6 kg/m² (mean±standard deviation [S])) followed for 2 years. Results: Surgically treated patients lost 28±15 kg and controls 0. 5±8. 9 kg (p<0. 0001). Two-year incidence of hypertension, diabetes, hyperinsulinemia, and lipid disturbances was compared in the two treatment groups. Adjusted odds ratios (95% CI) for the surgically treated group versus controls were 0. 38 (0. 22, 0. 65) for hypertension, 0. 02 (0. 00, 0. 16) for diabetes, 0. 10 (0. 03, 0. 28) for hyperinsulinemia, 0. 10 (0. 04, 0. 25) for hypertriglyceridemia, 0. 28 (0. 16, 0. 49) for low HDL-cholesterol and 1. 24 (0. 84, 1. 8) for hypercholesterolemia. Compared to controls, the 2-year recovery rates from hypertension, diabetes, hypo-HDL, and hypertriglyceridemia were significantly higher in the surgically treated group. Discussion: Intentional weight loss in the obese causes a marked reduction in the 2-year incidence of hypertension, diabetes and some lipid disturbances. The results suggest that severe obesity can and should be treated.     

Plasma levels of neurotensin in gastroplasty for morbid obesity

Fasting and postprandial plasma levels of the tridecapeptide neurotensin were determined in ten women before and three months after gastroplasty for morbid obesity. Measurements were by radioimmunoassay in unextracted plasma with two antisera recognizing intact neurotensin (NT1-13) or intact neurotensin together with small C-terminal fragments, which may circulate as metabolites of neurotensin. Levels of both intact neurotensin and C-terminal immunoreactivity in obese women were in the same order of magnitude as those found previously in lean persons. Fasting levels measured with both antisera were significantly reduced following gastroplasty (P less than 0.01). Meal-stimulated levels and increments were unchanged. The cause of this prolonged reduction is at present unknown, but may be a reduced luminal stimulation of the small intestine or an altered vagal tonus following gastroplasty.     

环境和遗传因素与慢性代谢性疾病的人群研究

几十年来我国居民经历了快速的营养转型,与不健康的膳食和生活方式相关的＂致肥环境＂,以及遗传倾向是导致我国慢性代谢性疾病如代谢综合征和2型糖尿病快速流行的主要推手。然而,我国目前非常缺乏针对导致慢性代谢性疾病的主要遗传和环境危险因素而开展的系统研究。在过去若干年中,通过开展基于社区人群的流行病学研究,本课题组发现了多个与代谢性疾病相关的基因变异、环境因素和生物标记物。与此同时,通过对代谢综合征或2型糖尿病患者进行的营养干预,发现添加亚麻子或其衍生物木酚素、核桃,以及用糙米替代白米能不同程度地改善代谢综合征或血糖控制。总之,所有努力旨在增进对导致中国人代谢性疾病高易感性相关的病因和机制的理解,同时也希望为疾病的预测和预防提供新的思路和线索。     

原发性高血压患者α-Adducin基因单核苷酸多态性(Gly460Trp)与血清胆红素含量相关性

探讨了自 2 0 0 0年 9月到 2 0 0 1年 1月来自安徽省霍邱县地区原发性高血压人群中α Adducin基因单核苷酸多态性与血清中总胆红素、直接胆红素和间接胆红素含量的相关性。在原发性高血压女性患者中 ,在校正了许多可能影响胆红素含量的重要因素后 ,与携带有Gly4 6 0Gly基因型的高血压女性患者相比较 ,携带有Trp4 6 0Trp基因型的高血压女性患者血清平均总胆红素 (β =- 1 2 μmol/L ;P =0 0 1)、直接胆红素 (β =- 0 4 μmol/L ;P =0 0 2 )和间接胆红素 (β=- 0 8μmol/L ;P =0 0 3)的含量比较低。在女性中抽取总胆红素、直接胆红素和间接胆红素含量最高和最低的各 2 5 % ,在校正了重要的变量后发现携带Trp/Trp基因型的女性比Gly4 6 0Gly基因型的女性有更大的可能性血清总胆红素含量 (OR值 =4 0 ;95 %可信区间 :1 6～ 10 2 ;P <0 0 1)、直接胆红素含量 (OR值 =4 0 ;95 %可信区间 :1 6～ 9 7;P <0 0 1)和间接胆红素含量 (OR值 =2 7;95 %可信区间 :1 1～ 6 7;P =0 0 3)更低。然而 ,在男性高血压患者中没有发现任何明显的相关性。以上的结果认为在中国原发性高血压女性患者中 ,Trp/Trp基因型与低的血清胆红素含量有直接关系 ,因为Trp/Trp基因型的女性的低血清胆红素 ,进而认为也许增加了患心血     

糖尿病大鼠心肌功能的改变及其机制*

目的:观察钙敏感受体(CaSR)表达变化在2型糖尿病大鼠心功能降低中的作用。方法:Wistar大鼠随机分成3组:对照组、糖尿病4周和8周组。糖尿病组大鼠给予高糖高脂饮食喂养,4周后腹腔注射链脲佐菌素建立2型糖尿病模型。通过HE染色观察心脏形态学变化,通过超声心动仪检测心脏功能的变化,通过Western blot检测心肌组织CaSR和PKC-α蛋白表达的变化。结果:与对照组相比,糖尿病大鼠心脏收缩和舒张功能降低,心肌组织出现不规则收缩带,且随着病程延长逐渐加重,同时心肌组织CaSR和PKC-α蛋白表达减少。结论:糖尿病大鼠心肌CaSR等蛋白的表达降低,从而引起细胞内钙紊乱,导致心功能下降。     

抗肥胖症和抗糖尿病新药

4 个新药——Contrave、Saxenda、Xultophy 和 Trulicity 在 2014 年 9 月份相继获批或推荐批准,分别用于治疗肥胖症和 2型糖尿病,可见糖尿病和肥胖症治疗领域迎来长足进展。分别介绍这 4 个新药及其开发历程与市场前景。