The role of vagally-mediated hyperinsulinemia in hypothalamic obesity

Evidence that the obesity syndrome which follows ventromedial hypothalamic (VMH) lesions is at least partially the result of a primary metabolic dysfunction is reviewed, as are proposals that the altered metabolism is due to enhanced vagally-mediated insulin release. This hypothesis was based largely on experiments demonstrating the complete reversal of hypothalamic obesity by subdiaphragmatic vagotomy, but subsequent studies have revealed that hypothalamic obesity is not always prevented by prior vagal transections. Interpretation of these discrepant results has been made difficult because of the frequent use of gastric secretion, behavioral, or other indirect tests for completeness of vagotomy. A review of more recent studies which have employed either direct assessment of vagotomy effects on insulin levels, pharmacological blockade of vagal efferent activity, or selective vagotomies indicates that vagally-mediated hyperinsulinemia can account for no more than 40% of the weight gain observed in animals with VMH lesions fed ad libitum, and may not be involved in the obesity that results from some parasagittal VMH knife cuts. It is concluded that vagally-mediated hyperinsulinemia does make a substantial, although not exclusive, contribution to the increased carcass lipid content observed in VMH animals that are food-restricted or pair-fed with control animals.     

c-Jun氨基末端激酶抑制剂减轻烫伤后胰岛素抵抗的实验研究

目的探讨c-Jun氨基末端激酶(JNK)抑制剂SP600125对烫伤后胰岛素抵抗的作用及机制。方法24只SD大鼠以表格随机法分为假伤组、烫伤对照组和烫伤 SP600125组。将大鼠制成30％TBSAⅢ度烫伤模型(其中假伤组以常温模拟烫伤过程)。伤后第4天进行葡萄糖钳夹实验(烫伤 SP600125组在实验开始前2 h给予拮抗剂SP600125),检测肌肉组织胰岛素受体底物(IRS)1磷酸化丝氨酸307(Ser307)和酪氨酸的活性变化,并比较各组磷酸化JNK表达水平。结果(1)葡萄糖钳夹实验:假伤组、烫伤对照组和烫伤 SP600125组100 g／L葡萄糖输注率分别为(12．33±0．42)、(6．61±0．27)、(11．11±0．68)mg·kg-1·min-1,各组间比较,差异有统计学意义(P< 0．01)。(2)烫伤对照组与假伤组比较,肌肉组织IRS-1磷酸化Ser307和磷酸化JNK活性明显升高, IRS-1磷酸化酪氨酸活性明显降低(P<0．05)。烫伤 SP600125组与烫伤对照组比较,肌肉组织中IRS-1磷酸化Ser307和磷酸化JNK活性降低而IRS-1磷酸化酪氨酸活性增加。结论SP600125通过抑制JNK磷酸化而降低IRS-1磷酸化Ser307活性,可部分减轻烫伤后胰岛素抵抗发生。     

高胰岛素血症对高血压病人血脂的影响

目的观察高胰岛素血症对高血压病人血脂的影响。方法将120例住院病人分为高血压病组(EH,60例)、高血压合并高胰岛素血症组(EH+高Ins组),比较两组患者血脂变化情况,并做分层分析。结果血浆高甘油三酯(TG)水平在高血压合并高胰岛素血症组中明显高于高血压病组(分别为2.35±1.05和1.59±0.68),并有显著性差异(P<0.01),血浆总胆固醇(TC)、低密度脂蛋白(LDL-c)、高密度脂蛋白(HDL-c)水平在两组中无显著性差异(P>0.05);女性患者的血浆TC在两组中明显高于同年龄组男性患者(P<0.05),但组间无显著性差异,血浆TG、LDL-c、HDL-c与性别和年龄无显著性差异(P>0.05)。结论高胰岛素血症使高血压病人血浆甘油三酯水平升高,且与性别和年龄关系不大。     

多囊卵巢综合征的高胰岛素血症与神经肽

对多囊卵巢综合征（ＰＣＯＳ）患者２０例及以已婚经产健康妇女１０名为对照组，行口服葡萄糖耐量试验（ＯＧＴＴ），以观察内源性神经肽及生长抑素（ＳＳ）的变化。结果：ＰＣＯＳ组空服血糖４．６３±０．６５ｍｍｏ１／Ｌ，ＯＧＴＴ后，有显著高血糖反应；空腹胰岛素（ＩＮＳ）与空腹β－内啡肽（β－ＥＰ）浓度及ＯＧＴＴ后ＩＮＳ净增量（平均为１８３．４４±４７．２８ｍＵ／Ｌ与β－ＥＰ净增量呈正相关（ｒ＝０．４９，Ｐ＜０．０５；ｒ＝０．３７，Ｐ＜０．０５）；ＯＧＴＴ后ＩＮＳ净增量与强啡肽（ＤｙｎＡ）净增量亦呈正相关（ｒ＝０．５８，Ｐ＜０．０１）；ＰＣＯＳ组空腹ＳＳ显著低于对照组（分别为１５６．０９±９４．０３及２１７．１４±６１．６３ｎｇ／Ｌ，Ｐ＜０．０１），但ＯＧＴＴ后两组ＳＳ浓度相似。表明：ＰＣＯＳ患者ＯＧＴＴ后糖代谢变化是一种特殊的糖耐量曲线；空腹高ＩＮＳ与ＳＳ抑制程度不足有关，而ＯＧＴＴ后高ＩＮＳ与β－ＥＰ，ＤｙｎＡ刺激程度过强有关。     

胰岛素与内皮细胞功能研究进展

胰岛素作为一个重要的代谢调节激素,还具有保护血管内皮细胞的作用,其作用机制可能为:调节血管内皮因子,抑制内皮细胞的收缩、增强内皮细胞间的紧密连接,防止动脉粥样硬化,调节内皮细胞的生长及活性氧簇(ROS)的表达.因此,胰岛素抵抗和高胰岛素血症导致的胰岛素信号紊乱将减弱胰岛素对内皮细胞的保护作用.然而,胰岛素是否可以成为糖尿病、肥胖等代谢性疾病慢性血管并发症的治疗药物,有待进一步研究.     

糖尿病与肿瘤关系的研究进展

2型糖尿病和肿瘤是两类严重威胁人类健康的慢性疾病。大量的流行病学和临床研究表明,2型糖尿病患者肝癌、胰腺癌、子宫内膜癌、胆囊癌、结直肠癌和乳腺癌的风险增加。高血糖可通过多种直接和间接机制促进癌细胞增殖、迁移、侵袭和免疫逃逸。胰岛素抵抗和高胰岛素血症会通过胰岛素/IGF-I信号轴激活多条信号通路促进肿瘤发生。持续的慢性炎性反应可通过DNA损伤和促炎因子促进癌症的发生发展。肠道菌群失调主要与几种消化道肿瘤发生密切相关。本文将对2型糖尿病与恶性肿瘤发生发展的关系及可能的机制研究进展进行综述。     

Insulin resistance and chronic liver disease

Increased insulin resistance is frequently associated with chronic liver disease and is a pathophysiological feature of hepatogenous diabetes.Distinctive factors including hepatic parenchymal cell damage,portalsystemic shunting and hepatitis C virus are responsible for the development of hepatogenous insulin resistance/diabetes.Although it remains unclear whether insulin secretion from pancreatic beta cells is impaired as it is in type 2 diabetes,retinopathic and cardiovascular risk is low and major causes of death in cirrhotic patients with diabetes are liver failure,hepatocellular carcinoma and gastrointestinal hemorrhage.Hemoglobin A1c is an inaccurate marker for the assessment and management of hepatogenous diabetes.Moreover,exogenous insulin or sulfonylureas may be harmful because these agents may promote hepatocarcinogenesis.Thus,pathogenesis,cause of death,assessment and therapeutic strategy for hepatogenous insulin resistance/diabetes differ from those for lifestyle-related type 2 diabetes.In this article,we review features of insulin resistance in relationship to chronic liver disease.We also discuss the impact of anti-diabetic agents on interferon treatment and hepatocarcinogenesis.     

正常血糖-高胰岛素血症的研究进展

高胰岛素血症是胰岛素抵抗人群为了维持血糖调节平衡的一种代偿表现,与正常血糖-非高胰岛素血症人群相比,其胰岛β细胞功能已经降低,心脑血管疾病的发病率增加,更容易发展成为2型糖尿病或葡萄糖调节受损的状态。控制体质量,适当的运动,服用双胍类及噻唑烷二酮类药物均可通过改善胰岛素敏感性来减轻胰岛β细胞的负荷,从而降低胰岛素水平。     

高胰岛素血症对冠心病患者血浆视黄醇结合蛋白4水平的影响及其临床意义

目的 观察视黄醇结合蛋白4(RBP4)在合并高胰岛素血症的冠心病患者血浆中的水平,探讨高胰岛素血症对冠心病患者RBP4的影响及其临床意义.方法 收集2009年9月～2010年5月在湘雅医院心血管内科住院并行冠状动脉造影( CAG)检查证实为冠心病患者59例,根据其胰岛素水平分为:单纯冠心病组(CHD)30例、冠心病合并高胰岛素组患者(CHD+HIn )29例;另选同期来我院行健康体检者作为正常对照组( NC )30例.酶联免疫吸附法(ELISA)检测上述人群血浆RBP4水平;测身高、体重,计算体重指数(BMI),测腰围、臀围,计算腰/臀,测收缩压与舒张压;测空腹血糖、胰岛素、餐后2h胰岛素,计算胰岛素抵抗指数(HOMA-IR),测血脂水平以及高敏C反应蛋白、尿酸、游离脂肪酸等生化指标.结果 CHD+HIn组患者血浆RBP4水平显著高于CHD组和NC组(P＜0.01),CHD与NC组间差异无统计学意义;相关分析显示RBP4与BMI、FPG、FIn、2bPIn、HOMA-IR、TG、HDL-C、UA、hsCRP有显著相关性;多元回归分析显示BMI、2hPIn、HOMA-IR是RBP4的独立相关因素.结论 合并高胰岛素血症的冠心病患者血浆RBP4水平显著升高,提示高胰岛素血症是影响RBP4的重要因素,RBP4可作为识别冠心病患者是否存在胰岛素抵抗的血清学指标;血浆RBP4与BMI、血脂、尿酸、等心血管危险因素相关,提示RBP4参与AS的发生、发展过程;BMI、2hPIn、HOMA-IR是RBP4的独立相关因素.     

The quantitative insulin sensitivity check index is not able to detect early metabolic alterations in young patients with polycystic ovarian syndrome

Objective.?To verify whether QUICKY is a suitable method for the identification of metabolic deterioration in normal weight patients affected by polycystic ovarian syndrome (PCOS).

Design.?Prospective clinical study.

Patient(s).?Seventy-nine PCOS normal weight adolescent subjects, 50 eumenorrheic, normal weight, non-hirsute controls matched for age and BMI.

Method(s).?Quantitative insulin sensitivity check index (QUICKY) and integrated secretory area under the curve of insulin values (I-AUC) during oral glucose tolerance test were calculated.

Result(s).?Seventy-nine PCOS and 50 controls were studied. Normal insulin sensitivity was defined as upper control 95th percentile by QUICKY values?<0.31, I-AUC at 180?min?<?16,645. When applying the calculated I-AUC cut-off, 41 PCOS were classified as normoinsulinemic and 38 as hyperinsulinemic, whereas using the calculated QUICKY cut-off, only 19 PCOS could be classified as insulin resistant (IR). Fifteen out of the 60 non-IR PCOS presented hyperinsulinemia; fasting glucose and insulin levels and QUICKY were not sufficient to identify these subjects. Thus, QUICKY displayed a low sensitivity (44%) and specificity (91%) in the diagnosis of the metabolic disorder disclosed by I-AUC.

Conclusions.?In young normal weight patients with PCOS the prevalence of early alterations of insulin metabolism are not detectable by QUICKY studies.