机械生长因子E肽的功能及研究展望

机械生长因子(MGF)E肽是胰岛素样生长因子Ⅰ(IGF-Ⅰ)基因剪接后的一段长40个氨基酸残基的延伸肽,其编码基因由IGF-Ⅰ基因的外显子5、6及部分外显子4组成。近年来的实验证明,MGFE肽能独立发挥促进肌肉肥大、修复肌肉损伤、保护神经元、提高心脏功能等多种重要的生理作用,有望对肌肉萎缩、肌营养不良、神经退行性疾病及大脑局部缺血等相关病症的新型药物开发产生重大推动,引起了国内外学者的广泛关注。     

胰岛素样生长因子家族与肺癌

胰岛素样生长因子(IGFs)家族与多种肿瘤的发生发展关系密切。本文综述了IGFs和胰岛素样生长因子受体(IGFRs)以及胰岛素样生长因子结合蛋白(IGFBPs)在肺癌发生发展、增殖、侵袭、转移和凋亡中所起的作用及其作用机制。为肺癌的预防、治疗、预后提供新的思路。     

碱性成纤维细胞生长因子与中枢神经元的功能

本文主要介绍bFGF在中枢神经元的多种功能及应用前景。bFGF作为多功能生长因子不仅可促进神经元存活,轴突生长,再生,保护神经元避免毒物损伤,而且还可促进移植神经元存活,调节神经元突触传递功能,发挥宽刘经递质,调质作用等,并具有明显的神经保护作用。为此bFGF可能在治疗进行性神经退行性疾病中起重要作用,如治疗阿尔茨海默病,帕金森病等。     

成纤维细胞生长因子对神经元的营养作用

成纤维细胞生长因子是一类多功能的多肽生长因子。近年来的研究表明,ＦＧＦ成神经系统的生长发育有十分密切的关系。ＦＧＦ体外能促进多种神经元的存活及突起生长,体内也能促进受损伤神经元的修复与再生,是一类新的神经营养因子。ＦＧＦ还与许多中枢神经系统疾病。如Ｐａｒｋｉｎｓｏｎ＇ｓ病、Ａｌｚｈｅｉｍｅｒ＇ｓ病的发生发展有关,因此深入开展ＦＧＦ神经营养作用的研究具有十分重要的意义。     

血管内皮生长因子的神经保护作用

血管内皮生长因子（vascular endothelial growth factor,VEGF）是内皮细胞特异性的生长因子,大多数关于VEGF的研究都是致力于其在血管生长方面的作用,而近年来有大量文献报道VEGF具有神经营养和促神经发生作用,它能够直接作用于神经元细胞和神经胶质细胞甚至是神经干细胞,促进其生长及存活。VEGF的多种功能使其和多种神经退行性疾病相关,如阿茨海默病,肌萎缩侧索硬化症,帕金森病等。导入VEGF基因能够改善肌萎缩侧索硬化症、帕金森病动物模型的病情。     

IGF-1介导的炎症反应在视网膜退行性疾病中的作用

视网膜退行性疾病是威胁老年人群视力最常见的疾病之一,目前关于引起该疾病的确切机制尚不清楚。近年来,有关胰岛素样生长因子-1(insulin like growth factor-1, IGF-1)等多种生长因子参与该疾病的病理生理机制的观点日益受到人们重视。有研究显示,IGF-1与视网膜退行性疾病的早期标志—神经炎症的发展存在密切联系,并有望成为治疗视网膜退行性疾病的重要靶向因子。本文将介绍IGF-1在视网膜退行性疾病炎症反应中的作用进展,为视网膜疾病的治疗方案提供新的思路。     

脉络丛上皮细胞及其神经保护作用

将神经营养因子和生长因子注射到脑损伤区域治疗神经系统变性病和急性脑损伤被证实有效,因此向脑损伤区域移植能够持续释放治疗因子的细胞可能成为一种新兴的治疗脑损伤的方法。脉络丛上皮细胞(CPECs)是构成脉络丛的主要结构成分,不仅参与合成脑脊液和构成血脑脊液屏障,而且能够分泌多种生物活性肽,包括神经营养因子,生长因子以及转运蛋白等。因此移植CPECs可能成为神经系统疾病具有前景的治疗方法。大量的文献已经证实,不管是体外研究还是在体水平,CPECs治疗能够促进神经元生长和增殖,对多种神经系统疾病产生疗效,具有神经保护作用。本文将对CPECs的神经保护作用做一综述,便于今后更好开展工作。     

胰岛素样生长因子的发现及其生理作用

胰岛素样生长因子的发现及其生理作用贺淹才（江西农业大学畜牧兽医学院,南昌３３００４５）关键词胰岛素样生长因子（ＩＧＦ）近年来,动物血液中的许多生长因子对动物生长、代谢的调节作用引起了人们极大兴趣。这些血浆中的生长因子有：胰岛素样生长因子（ＩＧＦ）、成...     

胰岛素样生长因子系统的营养调控

胰岛素样生长因子系统的营养调控邹仕庚王恬（南京农业大学动物科技学院,南京２１００９５）胰岛素样生长因子（ＩＧＦ）因其结构和功能类似胰岛素而得名,ＩＧＦ主要包括ＩＧＦⅠ和ＩＧＦⅡ。体内多种组织都能合成ＩＧＦ,表达ＩＧＦ受体;ＩＧＦ大部分由肝脏合成,...     

一种可分泌多种活化型因子的工程细胞的建立

该研究目的是构建可分泌多种活化型因子的工程细胞,用于诱导干细胞分化为耳蜗神经元样细胞的共培养。首先将大鼠脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)和神经营养因子3(neurotrophin 3, NT3)的成熟肽编码序列用内部核糖体进入位点序列(internal ribosome entry site, IRES)连接起来,再插入慢病毒表达载体pLVX-IRES-tdTomato,并包装成慢病毒,再将慢病毒分别感染HEK293T细胞和已有的表达活化型表皮生长因子(epidermal growth factor,EGF)、胰岛素样生长因子1(insulin-like growth factor 1, IGF1)和成纤维细胞生长因子2(fibroblast growth factor 2, FGF2)的HEK293T/3GF细胞,采用有限稀释法获得稳定转染的细胞克隆,利用Western blot检测细胞培养液上清中的BDNF和NT3的表达情况,并通过检测人肺癌A549细胞和大鼠嗜铬细胞瘤PC-12细胞的增殖以及PC-12细胞的分化情...     

Potential role of insulin on the pathogenesis of depression

The regulation of insulin on depression and depression‐like behaviour has been widely reported. Insulin and activation of its receptor can promote learning and memory, affect the hypothalamic‐pituitary‐adrenal axis (HPA) balance, regulate the secretion of neurotrophic factors and neurotransmitters, interact with gastrointestinal microbiome, exert neuroprotective effects and have an impact on depression. However, the role of insulin on depression remains largely unclear. Therefore, in this review, we summarized the potential role of insulin on depression. It may provide new insight for clarifying role of insulin on the pathogenesis of depression.     

Correlations of insulin resistance and neoplasms

Insulin resistance is a worldwide risk factor for the two most dangerous human disease groups; namely, for cardiovascular lesions and malignancies. The insulin resistance syndrome have five basic criteria: hyperglycemia, visceral obesity, elevated serum triglyceride level, low HDL-cholesterol level (dyslipidemia) and hypertension. Each of these criteria alone are risk factors for cancer, and they mean together a multiple risk. Insulin resistance of the liver, skeletal muscles, and fatty tissue leads to a reactive hyperinsulinemia by the increased secretory activity of the beta-cells. Insulin has diverse metabolic effects, and at the same time is a growth factor. It enhances the production and mitogenic activity of other, insulin-like growth factors, and leads to pathological cell proliferation. In the uncompensated phase of insulin resistance hyperglycemia appears, which promotes tumor genesis by several pathways. The elevated serum glucose level is advantageous for the increased DNA synthesis of the tumor cells. It provokes deliberation of free radicals, which will cause derangement of both the DNA and the enzymes having a role in the repair mechanisms. Hyperglycemia leads to a nonenzymatic glycation of protein structures, and the glycated products enhance the deliberation of free radicals, cytokines and growth factors. Insulin resistance means an enhanced risk for breast, pancreas, liver, colon, bladder, prostate and oral cavity cancers. The moderately increased fasting glucose level is also a risk factor for breast, stomach and colon cancers, even without manifestation of type 2 diabetes. Insulin resistance promotes tumor progression as well. In cancer patients with hyperglycemia or type 2 diabetes, the rate of tumor recurrence, metastatic spread and fatal outcome is higher as compared with the tumor patients without metabolic disease. The correlation between insulin resistance and tumor promotion reveals new possibilities in the prevention and treatment of cancer. The healthy diet, physical activity and weight loss increase insulin sensitivity, and decrease the risk for both cardiovascular diseases and malignancies.     

New insights into the pathogenesis of insulin resistance in humans using magnetic resonance spectroscopy

Insulin resistance plays a major role in the pathogenesis of type 2 diabetes, yet despite much effort, the underlying factors that are responsible for it are poorly understood. In this review, we focus on some recent advances in our understanding of the pathogenesis of insulin resistance in humans that have been made using magnetic resonance spectroscopy.     

Brain Insulin Dysregulation: Implication for Neurological and Neuropsychiatric Disorders

Arduous efforts have been made in the last three decades to elucidate the role of insulin in the brain. A growing number of evidences show that insulin is involved in several physiological function of the brain such as food intake and weight control, reproduction, learning and memory, neuromodulation and neuroprotection. In addition, it is now clear that insulin and insulin disturbances particularly diabetes mellitus may contribute or in some cases play the main role in development and progression of neurodegenerative and neuropsychiatric disorders. Focusing on the molecular mechanisms, this review summarizes the recent findings on the involvement of insulin dysfunction in neurological disorders like Alzheimer’s disease, Parkinson’s disease and Huntington’s disease and also mental disorders like depression and psychosis sharing features of neuroinflammation and neurodegeneration.     

Resistance to trophic neurite outgrowth of sensory neurons exposed to insulin

Insulin offers trophic support through receptors expressed widely on peripheral neurons. In this work, we studied whether peripheral sensory neurons demonstrate resistance to its trophic properties, a property relevant during type 2 diabetes mellitus or following supraphysiological therapy. Insulin receptors were not only localized to neuronal membranes and cytoplasm but also had a unique, previously unrecognized localization to neuronal nuclei. We confirmed that nanomolar doses increased neurite outgrowth of adult sensory neurons, but in response to micromolar doses of insulin, even following a brief 2-h exposure, survival and outgrowth of neurites were blunted. Neurons exposed to picomolar insulin concentrations in their media for 5 days had resistance to the impact of later nanomolar doses of insulin. Using a stripe assay seeded with insulin, neurites were more likely to reject higher doses of insulin. Insulin down-regulated mRNAs of the insulin receptor β subunit and up-regulated levels of GSK-3β, both potential mechanisms of insulin resistance, while down-regulating the protein expression of pAkt and pGSK-3β. Overall, these studies identify neuronal nuclear targeting of insulin and evidence for insulin-induced resistance to its trophic properties. The findings have implications for the understanding of the actions of insulin in the treatment of diabetes and neurological disorders.     

Integration of physiological mechanisms that influence fertility in dairy cows

Fertility in dairy cows has been declining for the past three decades. Genetic selection for increased milk production has been associated with changes in key metabolic hormones (growth hormone, insulin, IGF and leptin) that regulate metabolism by homoeostasis and homeorhesis. These metabolic hormones, particularly insulin, provide signals to the reproductive system so that regulation of ovarian function is coordinated with changes in metabolic status. Studies have shown, for example, that increasing circulating insulin concentrations during the early post partum period can advance the resumption of oestrous cycles by enhancing follicular growth. However, high concentrations of insulin can be detrimental to the developmental competence of oocytes, which is also influenced by the supply of fatty acids at the systemic level and at the ovarian level. Insulin status is also associated with the incidence and characteristics of abnormal ovarian cycles. These changes can occur without significant variation in circulating gonadotrophin concentrations. This suggests that additional factors, such as peripheral metabolites, metabolic hormones and locally produced growth factors, may have a modulating role. Recent evidence has demonstrated that ovarian responses to metabolic signals and nutrient profile vary according to the stage of the reproductive cycle. Improved understanding of this multifactorial process enables nutrition to be matched to genotype and milk production, with a positive impact on pregnancy rate.     

Activation of mRNA translation in rat cardiac myocytes by insulin involves multiple rapamycin-sensitive steps

Insulin acutely activates protein synthesis in ventricular cardiomyocytes from adult rats. In this study, we have established the methodology for studying the regulation of the signaling pathways and translation factors that may be involved in this response and have examined the effects of acute insulin treatment on them. Insulin rapidly activated the 70-kDa ribosomal S6 kinase (p70 S6k), and this effect was inhibited both by rapamycin and by inhibitors of phosphatidylinositol 3-kinase. The activation of p70 S6k is mediated by a signaling pathway involving the mammalian target of rapamycin (mTOR), which also modulates other translation factors. These include the eukaryotic initiation factor (eIF) 4E binding proteins (4E-BPs) and eukaryotic elongation factor 2 (eEF2). Insulin caused phosphorylation of 4E-BP1 and induced its dissociation from eIF4E, and these effects were also blocked by rapamycin. Concomitant with this, insulin increased the binding of eIF4E to eIF4G. Insulin also activated protein kinase B (PKB), which may lie upstream of p70 S6k and 4E-BP1, with the activation of the different isoforms being in the order alpha>beta>gamma. Insulin also caused inhibition of glycogen synthase kinase 3, which lies downstream of PKB, and of eEF2 kinase. The phosphorylation of eEF2 itself was also decreased by insulin, and this effect and the inactivation of eEF2 kinase were attenuated by rapamycin. The activation of overall protein synthesis by insulin in cardiomyocytes was substantially inhibited by rapamycin (but not by inhibitors of other specific signaling pathways, e.g., mitogen-activated protein kinase), showing that signaling events linked to mTOR play a major role in the control of translation by insulin in this cell type.     

Pharmacological approach in the treatment of insulin resistance.

Insulin resistance syndromes are heterogeneous in either severity or mechanism. Many drugs have been shown to counteract various elements of insulin resistance. Some of them, by normalization of metabolic parameters, decrease insulin resistance induced by chronic hyperglycemia in diabetes. Insulin and, to some extent, sulfonylureas are in this group, but these drugs are not stricto sensu medication of insulin resistance. Some drugs sensitize peripheral tissues to the action of insulin. For instance, biguanides and thiazolidine-dione facilitate translocation to the membrane of glucose transporter in presence of insulin. Other compounds as vanadate or IGF-1 mimic some peripheral action of insulin. Finally, blockade of FFA oxidation by specific inhibitors (methylpalmoxyrate) can limit insulin resistance. In 1992, among these compounds, specific of insulin resistance, biguanides are mostly used. However, the efficacy of these drugs is moderate and limited to type 2 diabetes.