抵抗素诱导肥胖机体胰岛素抵抗的炎症机制

抵抗素是一种脂肪因子,被证明与胰岛素抵抗密切相关,但其作用机制尚不明确。近年研究表明抵抗素参与了肥胖有关的炎症进程,对胰岛素敏感组织(脂肪、肝脏)炎症状态起到重要调控作用。肥胖诱导的慢性低度炎症是导致机体胰岛素抵抗的重要因素,抵抗素通过对炎症的调控参与肥胖机体胰岛素抵抗的发生。本文主要从组织及分子层面探讨抵抗素诱导胰岛素抵抗的炎症机制,为进一步了解抵抗素在肥胖相关疾病病理机制中的作用提供一些思路。     

抵抗素的生物学作用及调节机制

抵抗素的研究备受关注,是RELMs家族成员,与糖代谢、脂肪代谢、胰岛素抵抗等有很大关系。年龄、性别、营养状况、激素、各种细胞因子都对抵抗素mRNA的表达具有调节作用,奶牛抵抗素的研究目前也受到重视。     

综述PKR与胰岛素抵抗

胰岛素抵抗是2型糖尿病重要的发病机制之一。脂类、氧化应激及炎症因子等的刺激会导致胰岛素受体底物IRS的丝氨酸磷酸化,阻碍正常的酪氨酸磷酸化从而导致胰岛素与其受体结合并激活下游底物的P13K能力下降,减弱了胰岛素信号转导,引起胰岛素抵抗。越来越多研究表明,PKR(double-stranded RNA-dependent protein kinase)在肥胖状态及脂类、炎症因子刺激下能够被激活,活化的PKR能通过激活IKKβ和JNK使IRS1的丝氨酸磷酸化升高,使IRS1的酪氨酸磷酸化减少从而阻碍了胰岛素的PI3K途径从而引起胰岛素抵抗。本文综述了最新研究结果,阐明了PKR在胰岛素抵抗中发挥的重要作用。     

围生期能量负平衡奶牛胰岛素抵抗的研究进展

围生期奶牛能量负平衡可引起脂代谢紊乱并常伴有胰岛素抵抗,而胰岛素抵抗又进一步促进了脂代谢紊乱和能量负平衡。胰岛素抵抗是奶牛能量代谢性疾病酮病和脂肪肝的病理学基础,胰岛素抵抗奶牛主要临床特征是高非酯化脂肪酸血症、高酮血症和低胰岛素敏感性指数。高产奶牛易发生能量代谢性疾病,造成巨大经济损失。炎症、内质网应激和线粒体功能紊乱参与了胰岛素抵抗的发生。文章综述了奶牛胰岛素抵抗与能量代谢障碍性疾病之间的研究进展。     

胰岛素抵抗机制及其营养干预作用研究

胰岛素抵抗(Insulin resistance,IR)常会引发血脂异常、非酒精性脂肪肝等慢性代谢疾病,影响动物正常生长状态并降低养殖效益。机体存在多种能够诱发胰岛素抵抗的因素,如氧化还原状态、体脂代谢和肠道微生物的种类和数量等,明确这些影响因素的作用及其作用机制对寻找改善胰岛素抵抗的作用靶点和营养物质具有重大意义。目前,许多营养干预措施已用于胰岛素抵抗的干预研究,该文对畜禽胰岛素抵抗的机制、危害及其干预作用做进行综述,以期为改善胰岛素抵抗提供理论基础和实践依据。     

重组牛抵抗素对鼠血糖和胰岛素含量的影响

为了研究重组牛抵抗素对小鼠血液中血糖和胰岛素含量的影响,选取体质量相似的4周龄wistar大鼠20只,随机分成4组,分别在禁食2d和自由进食的情况下注射PBS缓冲液和重组牛抵抗素,12h1次,连续4次。随后在0、15、30、60、120、180min分别尾静脉采血,检测血糖和胰岛素含量。试验结果表明重组牛抵抗素不论对自由进食或禁食2d大鼠的血糖浓度和胰岛素水平均具明显提高作用,说明重组牛抵抗素具有明显的生物学活性。     

FoxOs转录因子对机体代谢的调控

Forkhead box O(Foxos)转录因子在调控机体代谢中发挥重要作用,在种属间高度保守,并受胰岛素信号控制.FoxOs在胰岛素敏感组织如肝脏、胰腺、骨骼肌和胃肠道中表达.在机体能量摄入受限或饥饿状态下,FoxOs位于细胞核内,激活相关基因转录,增加肝脏葡萄糖产生,减少胰岛素分泌,增加采食量,引起骨骼肌降解,为葡萄糖异生提供底物;然而在能量摄入过多或胰岛素抵抗时FoxOs被激活,失去转录调节活性;同时,FoxOs还参与调控细胞分化、增殖和细胞存活.本文综述了FoxOs转录因子控制胰岛素敏感组织中相关基因表达,从而调控机体代谢和组织发育.了解FoxOs转录因子的功能和作用机制,将为调控激素敏感组织发育和机体能量代谢提供依据.     

黄烷醇对动物胰岛素抵抗状态下血糖稳态的调控作用及其机理

血糖稳态对动物机体各项生理功能的正常发挥起着重要作用。黄烷醇是一类来源于植物的生物类黄酮物质,研究表明,黄烷醇可以平衡动物胰岛素抵抗状态下的血糖稳态,其机制可能涉及调节肠道碳水化合物的消化吸收效率、增加胰高血糖素样肽-1的活性、促进胰岛β细胞分泌胰岛素、提升肝糖原合成效率以及降低机体炎症来保护胰岛素信号转导途径不被破坏等方面。本文将黄烷醇对动物胰岛素抵抗状态下血糖稳态的调控作用及其机理作一概述,为其在生产和临床上的应用提供依据。     

抵抗素与动物肌内脂肪沉积研究进展

抵抗素是一种脂肪组织特异分泌的多肽类激素,对啮齿动物和人类有多效性作用。抵抗素分泌来源和抵抗素功能的多样性有很大差异。随着人们对抵抗素功能的不断深入了解,其在调控动物糖脂代谢与肌内脂肪沉积等方面的作用逐渐成为研究热点。文章综述抵抗素的作用机制及其对脂肪代谢的调控和肌内脂肪沉积等方面的影响。     

miRNAs在糖尿病心血管疾病中的作用

糖尿病是全球最常见的代谢紊乱综合征,被公认为健康最重要的威胁之一.而miRNAs在糖尿病心血管疾病、胰岛素抵抗、糖尿病肾病、肥胖及脂代谢等并发症的发生发展中具有重要的作用.因此本文综述近几年与糖尿病心血管有关的miRNAs的作用机制及功能意义的研究进展,有助于我们进一步了解糖尿病引起的心血管疾病的病理生理机制,为糖尿病心血管疾病的诊断和治疗提供新的思路和理论基础.     

Cloning and characterization of porcine resistin gene

Resistin is a member of resistin-like molecules (RELMs) and a hormone secreted from mature adipocytes in rodents and leukocytes in human. We now report the cloning and characterization of the full-length porcine resistin cDNA and gene. Sequence analysis indicated that the pig resistin cDNA sequence had an open reading frame of 330 bp encoding a 12 kDa protein of 109 amino acids. The deduced amino acid sequence showed 75.2% identity to the human resistin. The porcine resistin gene was composed of four exons and had exactly the same exon structure as the human resistin gene. The tissue distribution of porcine resistin mRNA was assessed by semi-quantitative RT-PCR. Resistin gene expression was the highest in porcine leukocytes and low in adipose tissue. Resistin protein could be detected in porcine serum by western blotting and it circulated in serum as dimers and trimers. We provided the first evidence that resistin was abundantly expressed in porcine leukocytes and had an expression pattern similar to that in human resistin mRNA and protein. This suggests that the pig may be a suitable animal model for studying the function of resistin in human insulin resistance.     

抗素的研究进展

从抗素的发现、家族成员、结构、生物学功能、基因表达调控等方面论述了抗素在生物化学和遗传学方面的最新研究进展。认为抗素的浓度与胰岛素活性紧密相关；抗素基因的表达受多种激素、药物、营养状态的调控；其功能与糖代谢、脂代谢及动脉硬化的形成有关。     

Signals of adiposity

Adipose tissue, a reserve of energy, has played an essential role in mammalian evolution. Adipose tissue differs from other tissues in that its mass has considerable capacity to expand, which while beneficial in decreasing the risk of starvation, increases the risk of predation. Adipose tissue mass is thus under tight control in nondomestic species. Adipose tissue secretes a variety of factors, some of which (leptin, tumor necrosis factor (TNF) , resistin) are thought to be involved in modulation of adipose mass. Leptin has a variety of functions, primarily targetting the hypothalamus where it acts to decrease appetite and increase energy expenditure. Leptin is also involved in the adaptations to fasting, and leptin is also required for normal reproductive and immune function. TNF and resistin appear to have key paracrine roles, attenuating the anabolic effects of insulin on adipose tissue metabolism.     

Gene expression of resistin and TNF-α in adipose tissue of Japanese Black steers and Holstein steers

The aim of the present study was to compare the expression of adipose tissue mRNA related to glucose metabolism between Japanese Black steers (n = 5) and Holstein steers (n = 5). We examined the expression of the resistin, tumor necrosis factor‐α (TNF‐α), glucose transporter 1 (GLUT1) and growth hormone receptor (GHR) genes using real‐time polymerase chain reaction of cDNA in adipose tissue. The cDNA sequence identified by 5′/3′‐rapid amplification of cDNA and the deduced amino acid sequence were highly conserved in human, porcine and murine resistin. Expression of resistin mRNA was significantly greater in Holstein steers than in Japanese Black steers. In contrast, expression of TNF‐α mRNA was slightly greater in Japanese Black steers. Expression of GHR mRNA was significantly greater in Japanese Black steers compared with the Holstein steers, although there was no significant difference in the expression of GLUT1 mRNA. However, the plasma non‐esterified fatty acid (NEFA), glucose, insulin and growth hormone concentrations did not differ between Japanese Black and Holstein steers. The present results show that there is a difference in the expression level of mRNA related to glucose metabolism between Japanese Black steers and Holstein steers.     

Insulin resistance in equine digital vessel rings: an in vitro model to study vascular dysfunction in equine laminitis

Reasons for performing study: One of the causes of equine laminitis is hyperinsulinaemia, which may be associated with endothelial dysfunction and insulin resistance of vessels. Hypothesis and objectives: Insulin resistance can be induced in palmar digital vessels by continued exposure to insulin in vitro. The objective was to evaluate this in vitro model for future studies. Methods: Palmar digital vessel segments were collected immediately after euthanasia from horses with normal insulin/glucose blood values. Four arterial and 4 venous rings (3 mm wide) were prepared and each ring mounted in a tissue bath, containing Tyrode's solution at 37°C, 2 g tension was applied and the rings allowed to equilibrate for 45 min. Of the 4 rings of each vessel type, one was used as a control. One each of the remaining 3 rings was used for incubation with insulin (to induce resistance), wortmannin (to block PI3‐kinase) and PD‐098059 (to block MAP‐kinase), respectively, for 30 min. After the incubation period, the rings were contracted with phenylephrine. When the response reached a plateau, a single dose of insulin was added to the baths and the response of each ring monitored for 30 min. Results: Insulin relaxed the control rings and those treated with PD 098059 but contracted those pretreated with insulin and wortmannin. Normal relaxation responses of the rings were converted to contractions by insulin resistance. Insulin resistance was confirmed by the qualitative response of insulin‐incubated and wortmannin‐incubated rings. Conclusions: This study demonstrated successful induction of insulin resistance in both arterial and venous rings. It also suggested that the MAP‐kinase pathway plays a minor role in controlling vasomotor tone under normal physiological conditions. Potential relevance: The study suggests that the induction of insulin resistance in equine palmar digital vessel rings is reliable and provides a good in vitro model for studying the vascular insulin resistance which may occur in equine laminitis.     

Decreased gene expression of insulin signaling genes in insulin sensitive tissues of obese cats

Type 2 diabetes mellitus (DM) animal models have provided ample opportunity for investigating pathogenesis, as well as to evaluate novel treatment and prevention options for the disease. Because the domestic cat shares a similar environment with humans, it is also confronted with many similar risk factors for diabetes, such as physical inactivity and obesity. Obesity is a significant risk factor for diabetes in cats, and as such, the domestic cat may serve as an ideal model for investigating obesity induced insulin resistance. This study determined changes in insulin signaling genes within insulin sensitive tissues of obese felines. Quantitative RT-PCR was performed to determine mRNA levels of three important insulin signaling genes which have been implicated with insulin resistance: insulin receptor substrate (IRS)-1, IRS-2, and phosphatidylinositol 3’-kinase (PI3-K) p85α. Obese cats had significantly lower IRS-2 and PI3-K p85α mRNA levels in liver and skeletal muscle as compared to control cats. This down regulation of insulin signaling genes in obese cats mirrors that of obese humans and rodents suffering from insulin resistance. Interestingly, preprandial blood tests indicated that our obese cats were no different from control cats with regards to glucose tolerance and insulin resistance, thus indicating that the obese cats used in our study had a moderate level of obesity. Therefore, insulin signaling gene alterations were occurring in insulin sensitive tissues of moderately obese felines before glucose intolerance was clinically evident. As such, the monitoring of key insulin signaling genes may have some important diagnostic value to determine the risk level and degree of obesity induced insulin resistance.     

微量元素铬在动物上的研究与应用

铬是动物的必需微量元素之一,是葡萄糖耐量因子的重要活性组成成分,铬通过葡萄糖耐量因子(GTF)协同胰岛素的作用,影响碳水化合物、脂类、蛋白质和核酸代谢,进而影响动物的生长、免疫、繁殖和胴体品质,降低应激,改善机体免疫机能,提高畜禽生产性能和繁殖力。动物体内铬的研究已经取得了一定的进展,并且在动物上的应用也已经得到了实践证实。本文通过对铬的理化特性、铬在动物体内的吸收、运输、贮存和排泄、铬的生物学功能以及铬在动物生产性能上的作用、铬的需要量等方面进行了综合阐述,指出其广阔的应用前景及发展方向。收稿日期:2002-05-27基金项目:山西省归国留学基金项目(99044)作者简介:乔富强(1974-),男,山西农业大学动物科技学院在读硕士,主要从事动物营养与饲料科学的研究工作。