胰岛素样生长因子与老年高血压病的关系

目的　观察老年原发性高血压患者和同时伴有左室肥厚的患者血清胰岛素样生长因子 (IGF 1)水平以及两者之间的关系。方法　 6 0例高血压患者 ,分为 2组 ,单纯高血压组 ,高血压伴左室肥厚组 ,2组均做心脏超声心动图 ,用放射免疫法检测血清IGF 1,比较 2组IGF 1水平及与左室肥厚的关系。结果　 2组患者的血清IGF 1水平均高于对照组 (P <0 .0 0 1) ,同时IGF 1与左室肥厚有正相关关系。结论　IGF 1可能参与了高血压左室肥厚的形成过程     

初诊2型糖尿病患者胰岛素强化治疗对凝血功能的影响

目的观察初诊2型糖尿病患者经胰岛素强化治疗对凝血功能的影响。方法将新诊断的2型糖尿病患者使用胰岛素强化治疗前及治疗后3个月。分别抽取肘静脉血,进行凝血功能测定,取毛细血管血做糖化血红蛋白测定。结果初诊2型糖尿痛患者经胰岛素强化治疗后糖化血红蛋白（HbAlc）明显下降,凝血酶原时间（PT）延长、部分活化凝血活酶时间（删）延长、国际标准化比值（矾R）延长、凝血活酶时间（TT）无明显改变。结论初诊2型糖尿病患者短期胰岛素强化治疗有利于改善凝血功能。     

桑银降糖胶囊对链脲霉素致糖尿病大鼠的降糖作用

目的观察桑银降糖胶囊对链脲霉素（STZ）致糖尿病大鼠的降糖疗效。方法采用STZ制备糖尿病大鼠模型,随机分为糖尿病模型组、桑银降糖胶囊大剂量组（1．2g／kg）、桑银降糖胶囊小剂量组（0．3g／kg）、桑枝颗粒组各10只,另设对照组10只。采用微量血糖测试仪检测各组糖尿病大鼠血糖,125^I-胰岛素放射免疫试剂盒测血清胰岛素水平,同时进行HE染色观察各组大鼠的胰腺病理变化,电镜观察肾脏、肝脏超微结构的变化。结果与模型组比较,桑银降糖胶囊大剂量、小剂量组大鼠血糖降低、血清胰岛素水平升高（P均〈0．01）,其中桑银大剂量组的降糖作用较桑枝颗粒组明显（P〈0．01）。HE染色显示桑银大剂量组较模型组胰腺组织结构完好,细胞溶解、碎裂、浊肿、空泡样变等病理变化明显减少,胰岛数量及岛内细胞数量较多,结构清晰,淋巴细胞浸润减少。电镜结果显示桑银降糖胶囊可减轻糖尿病大鼠的肾脏、肝脏损伤。结论桑银降糖胶囊对STZ糖尿病大鼠有显著的降血糖作用,并对胰腺、肾脏、肝脏损伤具有一定的保护作用。     

肝硬化患者糖代谢异常及胰岛素抵抗的临床研究

目的　探讨肝硬化糖代谢异常及胰岛素抵抗的病因和机制。方法　对 2 8例肝硬化患者 ,30例正常人进行了空腹血糖 (FPG)、餐后 2小时血糖 (PPG)、血清空腹胰岛素 (FINS)的检测 ,计算胰岛素释放指数 (IRI)及胰岛素敏感指数 (ISI) ,对各项结果进行比较分析。结果　肝硬化组存在着糖耐量异常 ,餐后 2小时血糖、血清空腹胰岛素、胰岛素释放指数显著高于正常对照组 (P <0 .0 1)。胰岛素敏感指数 ,显著低于正常对照组 (P <0 .0 1)。肝硬化Child分级比较 ,随着病情加重 ,糖代谢紊乱逐渐突出。结论　肝硬化失代偿患者存在糖代谢异常 ,这种代谢异常和肝功能损害、胰岛素抵抗有关     

双时相门冬胰岛素30对2型糖尿病患者血糖的影响

目的分析2型糖尿病患者口服降糖药控制不满意时加用双时相门冬胰岛素30治疗前后血糖水平的变化,探讨其降糖作用。方法 40例2型糖尿病患者口服降糖药控制不满意时加用双时相门冬胰岛素30治疗24周,观察治疗前后血糖等指标的变化。结果双时相门冬胰岛素30治疗后空腹血糖(FPG)、餐后2 h血糖(PPG)、糖化血红蛋白(HbA1c)、甘油三酯(TG)水平较治疗前显著降低,患者加用双时相门冬胰岛素30治疗后,HbA1c水平<7%及≤6.5%者所占比例较治疗前显著增加。结论双时相门冬胰岛素30可改善口服降糖药控制不满意时2型糖尿病患者的血糖控制及血脂代谢,有助于降低2型糖尿病患者并发症,改善预后。     

血清RBP4与妊娠期糖尿病胰岛素抵抗关系

目的探讨血清视黄醇结合蛋白4（RBP4）水平与妊娠期糖尿病（GDM）胰岛素抵抗的关系。方法采用酶联免疫吸附法测定了30例GDM病人（GDM组）及30例糖耐量正常孕妇（对照组）血清RBP4水平,葡萄糖氧化酶法检测空腹血糖（FPG）,放射免疫法检测空腹胰岛素（FIN）,计算胰岛素抵抗指数（HOMA-IR）。结果 GDM组血清RBP4水平显著高于对照组（t=8.298,P〈0.05）。GDM组FPG、FIN及HOMA-IR水平明显高于对照组（t=7.259～16.409,P〈0.05）。GDM组血清RBP4水平与HOMA-IR呈明显正相关（r=0.744,P〈0.05）。结论 GDM病人血清RBP4水平升高,可能参与了糖尿病胰岛素抵抗的发生。     

Hepatitis C virus infection: molecular pathways to steatosis, insulin resistance and oxidative stress

The persistent infection with hepatitis C virus is a major cause of chronic liver disease worldwide. However, the morbidity associated with hepatitis C virus widely varies and depends on several host-related cofactors, such as age, gender, alcohol consumption, body weight, and co-infections. The objective of this review is to discuss three of these cofactors: steatosis, insulin resistance and oxidative stress. Although all may occur independently of HCV, a direct role of HCV infection in their pathogenesis has been reported. This review summarizes the current understanding and potential molecular pathways by which HCV contributes to their development.     

Impact of HCV genetic differences on pathobiology of disease

Multiple HCV genotypes have been isolated worldwide. Genotype seems to be involved in the main pathological aspects of HCV infection. Insulin resistance, steatosis and progression toward cirrhosis, fibrosis and hepatocellular carcinoma establish and develop following genotype-specific mechanisms. Moreover genotype influences pharmacological treatment in term of dose and duration. Pathways involved in cell proliferation, apoptosis, lipid metabolism, insulin and interferon signaling are impaired to a different extent among genotypes, leading to distinct pathological settings. Genotype 1 is associated with a more aggressive disease with increased insulin resistance, worst response to therapy, higher risk of cirrhosis and hepatocellular carcinoma development, while genotype 3 is associated with increased steatosis and fibrosis. The identification and characterization of HCV types and subtypes provides insight into the different outcome of HCV infection and responsiveness to therapy. In the present article, we focused on the pathogenicity of HCV genotypes and their effect on disease progression and treatment.     

Effects of sibutramine on abdominal fat mass, insulin resistance and blood pressure in obese hypertensive patients

OBJECTIVE: The objective of this study is to assess the effects of sibutramine on body weight, body fat distribution, insulin resistance, plasma leptin, lipid profile and blood pressure profiles in hypertensive obese patients. METHODS: Eighty-six central obese hypertensive patients (BMI = 39 +/- 5 kg/m(2), 84% of women, 48 +/- 8.5 years old) were placed on a hypocaloric diet and placebo therapy for 4 weeks. They were then randomized to receive sibutramine (10 mg) or placebo for 24 weeks. Both, before therapy and at the end of the study, the waist and hip circumferences were measured and the waist/hip ratio (WHR) was calculated; abdominal ultrasonography was performed in order to estimate the amount of subcutaneous fat (SF) and visceral fat (VF), and the visceral/subcutaneous ratio. Beyond HOMA-r, another insulin resistance index (IRIp) was calculated by means of the formula: peak of blood glucose after oral glucose load x plasma insulin level/10(4). Fasting plasma leptin and lipid levels were also determined. RESULTS: Sibutramine induced greater weight reduction than placebo (6.7 vs. 2.5%, p < 0.001). Reductions in WHR (0.97 +/- 0.08 vs. 0.94 +/- 0.07, p < 0.01), IRIp (0.11 +/- 0.07 vs. 0.09 +/- 0.06 mmol mu/l(2)) and VF (6.4 +/- 2.4-6.0 +/- 2.4 cm, p < 0.01) were observed only with sibutramine. Plasma leptin decreased with placebo (24 +/- 15 vs. 18 +/- 10 UI/l, p < 0.01), but not with sibutramine (18.8 +/- 8.4 vs. 18.2 +/- 13.2 UI/l). No clinically significant change in lipid profile was observed in both groups. Moreover, office and 24-h blood pressure values did not change during placebo or sibutramine therapy, whereas a significant increase in office heart rate, from 78.3 +/- 7.3-82 +/- 7.9 b.p.m., p = 0.02, was observed with sibutramine. CONCLUSIONS: Sibutramine therapy induced greater body weight loss than placebo in hypertensive obese patients. This was associated with WHR reduction, decreases in VF and insulin resistance. The maintenance of leptin levels during sibutramine therapy may be important to avoid weight recovery, although this finding must be confirmed by other prospective studies.     

Neprilysin inhibition in mouse islets enhances insulin secretion in a GLP-1 receptor dependent manner

ABSTRACT

Neprilysin, a widely expressed peptidase upregulated in type 2 diabetes, is capable of cleaving and inactivating the insulinotropic glucagon-like peptide-1 (GLP-1). Like dipeptidyl peptidase-4 (DPP-4), inhibition of neprilysin activity under diabetic conditions is associated with increased active GLP-1 levels and improved glycemic control. While neprilysin expression has been demonstrated in islets, its local contribution to GLP-1-mediated insulin secretion remains unknown. We investigated in vitro whether islet neprilysin inhibition enhances insulin secretion in response to glucose and/or exogenous GLP-1, and whether these effects are mediated by GLP-1 receptor (GLP-1R). Further, we compared the effect of neprilysin versus DPP-4 inhibition on insulin secretion. Isolated islets from wild-type (Glp1r^+/+) and GLP-1 receptor knockout (Glp1r^?/?) mice were incubated with or without the neprilysin inhibitor thiorphan and/or the DPP-4 inhibitor sitagliptin for 2.5 hours. During the last hour, insulin secretion was assessed in response to 2.8 mmol/l or 20 mmol/l glucose alone or plus exogenous active GLP-1. In Glp1r^+/+ islets, neprilysin inhibition enhanced 2.8 mmol/l and 20 mmol/l glucose- and GLP-1-mediated insulin secretion to the same extent as DPP-4 inhibition. These effects were blunted in Glp1r^?/? islets. In conclusion, inhibition of islet neprilysin in vitro increases glucose-mediated insulin secretion in a GLP-1R-dependent manner and enhances the insulinotropic effect of exogenous active GLP-1. Thus, neprilysin inhibitors may have therapeutic potential in type 2 diabetes by preserving islet-derived and circulating active GLP-1 levels.