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Management of Hypothalamic Obesity during Transition from Childhood to Adulthood. 儿童期到成年期下丘脑肥胖的处理。
Pub Date : 2018-01-01 Epub Date: 2018-06-08 DOI: 10.1159/000487526
Marion Bretault, Claire Carette, Charles Barsamian, Sébastien Czernichow

Hypothalamic obesity (HO) is a rare and serious disease of various origins: tumor, traumatism, radiotherapy, vascular, genetic, or even psychotropic drug use. HO usually begins in childhood with eating disorders and progresses with an aggregate of severe comorbidities. Transition from pediatric to adult health care is a critical period to assure weight stability and a good management of comorbidities. In case of loss to follow-up, there is an increased risk of major weight gain and long-term complications with severe obesity. To minimize this risk, pediatric and adult specialists must work together to prepare, supervise, and monitor transition. Transition ideally involves the patient, parents, and care providers with a good communication between pediatric and adult teams from expert centers. Maintaining a diet and physical activity management plan, acquisition of autonomy for hormone replacement therapy and management of psychosocial consequences of obesity are fundamental issues in patients with HO. Patient associations and specialized diet center weight loss programs can help as well as group approaches.

下丘脑肥胖(HO)是一种罕见而严重的疾病,其病因多种多样:肿瘤、创伤、放疗、血管、遗传,甚至精神药物的使用。HO通常在儿童期以饮食失调开始,并发展为严重的合并症。从儿科过渡到成人保健是一个关键时期,以确保体重稳定和良好的管理合并症。在随访失败的情况下,严重肥胖会增加体重增加和长期并发症的风险。为了尽量减少这种风险,儿科和成人专家必须共同努力,准备、监督和监测过渡。理想的过渡包括患者、家长和护理提供者,在专家中心的儿科和成人团队之间进行良好的沟通。维持饮食和身体活动管理计划,获得激素替代治疗的自主权和管理肥胖的社会心理后果是HO患者的基本问题。患者协会和专门的饮食中心减肥计划可以帮助以及小组方法。
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引用次数: 4
Transition of Care 护理过渡
Pub Date : 2017-10-30 DOI: 10.1159/isbn.978-3-318-06143-7
C. Corbett
Patients who called an AL between September 1, 2011 and September 1, 2012 and reported being hospitalized within 30 days. A 500-bed, university-affiliated hospital Prospective cohort of 308 unique patients who were hospitalized or had outpatient surgery within 30 days preceding the call Findings: 37% and 47% of calls occurred within 24 or 48 hours of discharge, respectively 63% came from surgery patients despite surgery patients accounting for only 38% of the discharges Most common issues were: uncontrolled pain questions about medications aftercare instructions (eg, the care of surgical wounds) 30-day readmissions and urgent or emergent care visits were higher for patients who called the AL than for those who did not (15% vs 4% and 30% vs 7%, respectively, both P < 0.0001, (sample sizes were too small to accommodate robust matching or multivariate analyses) Journal of Hospital Medicine 2014;9:695–699. © 2014 Society of Hospital Medicine Changes in Medical Errors after Implementation of a Handoff Program
在2011年9月1日至2012年9月31日期间致电AL并报告在30天内住院的患者。一个拥有500张床位的大学附属医院前瞻性队列,包括308名在呼叫前30天内住院或接受门诊手术的独特患者。结果:37%和47%的呼叫发生在出院后24或48小时内,尽管手术患者仅占出院人数的38%,但63%的患者来自手术患者。最常见的问题是:关于药物治疗后护理说明(如手术伤口护理)的不受控制的疼痛问题。30天的再次入院和紧急或紧急护理访视,呼叫AL的患者比没有呼叫AL的人更高(分别为15%对4%和30%对7%,均<0.0001,(样本量太小,无法进行稳健的匹配或多变量分析)《医院医学杂志》2014;9:695–699。©2014医院医学会实施交接计划后医疗错误的变化
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引用次数: 8
Ghrelin and Growth. 生长素和生长。
Pub Date : 2017-01-01 Epub Date: 2017-08-15 DOI: 10.1159/000475732
Reena Perchard, Peter E Clayton

Ghrelin is a pleiotropic hormone, whose effect on growth hormone secretion, through the growth hormone secretagogue (GHS) receptor, is one of its many actions. Relationships between GHS receptor gene variants and human height, both in healthy individuals and in patients with growth disorders have been identified. These include constitutional delay in growth and puberty, idiopathic short stature, and isolated growth hormone deficiency. In this review, we provide an overview of the role of ghrelin in growth.

胃饥饿素是一种多效性激素,其作用之一是通过促生长素(GHS)受体影响生长激素的分泌。已经确定了健康个体和生长障碍患者中GHS受体基因变异与人类身高之间的关系。这些包括生长发育和青春期的体质延迟,特发性身材矮小和孤立性生长激素缺乏症。在这篇综述中,我们提供了ghrelin在生长中的作用的概述。
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引用次数: 16
Just a Gut Feeling: Central Nervous Effects of Peripheral Gastrointestinal Hormones. 只是一种直觉:外周胃肠激素对中枢神经的影响。
Pub Date : 2017-01-01 Epub Date: 2017-08-15 DOI: 10.1159/000475734
Christian L Roth, Robert Patrick Doyle

Despite greater health education, obesity remains one of the greatest health challenges currently facing the world. The prevalence of obesity among children and adolescents and the rising rates of prediabetes and diabetes are of particular concern. A deep understanding of regulatory pathways and development of new anti-obesity drugs with increased efficacy and safety are of utmost necessity. The 2 major biological players in the regulation of food intake are the gut and the brain as peptides released from the gut in response to meals convey information about the energy needs to brain centers of energy homeostasis. There is evidence that gut hormones not only pass the blood-brain barrier and bind to receptors located in different brain areas relevant for body weight regulation, but some are also expressed in the brain as part of hedonic and homeostatic pathways. Regarding obesity interventions, the only truly effective treatment for obesity is bariatric surgery, the long-term benefits of which may actually involve increased activity of gut hormones including peptide YY3-36 and glucagon-like peptide 1. This review discusses critical gut-hormones involved in the regulation of food intake and energy homeostasis and their effects on peripheral tissues versus central nervous system actions.

尽管加强了健康教育,肥胖仍然是目前世界面临的最大健康挑战之一。儿童和青少年肥胖的流行以及糖尿病前期和糖尿病发病率的上升尤其令人担忧。深入了解调控途径,开发新的抗肥胖药物,提高疗效和安全性是非常必要的。调节食物摄入的两个主要生物角色是肠道和大脑,因为肠道在进食时释放的肽将能量需求的信息传递给大脑能量平衡中心。有证据表明,肠道激素不仅可以通过血脑屏障并与位于大脑不同区域的与体重调节相关的受体结合,而且一些激素还可以作为享乐和体内平衡途径的一部分在大脑中表达。关于肥胖干预,唯一真正有效的治疗方法是减肥手术,其长期益处实际上可能涉及增加肠道激素的活性,包括肽YY3-36和胰高血糖素样肽1。本文综述了参与调节食物摄入和能量稳态的关键肠道激素及其对外周组织和中枢神经系统活动的影响。
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引用次数: 4
Enteroendocrine Cells: Metabolic Relays between Microbes and Their Host. 肠内分泌细胞:微生物和宿主之间的代谢继电器。
Pub Date : 2017-01-01 Epub Date: 2017-08-15 DOI: 10.1159/000475736
Hubert Plovier, Patrice D Cani

Gut bacteria exert a variety of metabolic functions unavailable to the host and are increasingly seen as a virtual organ located inside our gastrointestinal tract. Scattered in our intestinal epithelium, enteroendocrine cells (EECs) regulate several aspects of the host's physiology and translate signals coming from the gut microbiota through their hormonal secretions. In this chapter, we will assess the interplay between the gut microbiota and EEC and its consequences for the physiology of the host. We will first describe alterations of different populations of EEC in germ-free animals. The role of mediators of this interaction, such as microbial metabolites and their receptors will also be discussed. Finally, different strategies harnessing host-microbe crosstalk for therapeutic purposes will be presented with an emphasis on obesity and related disorders.

肠道细菌发挥宿主无法获得的多种代谢功能,越来越多地被视为位于我们胃肠道内的虚拟器官。肠内分泌细胞(EECs)分散在我们的肠上皮中,调节宿主生理的几个方面,并通过它们的激素分泌来翻译来自肠道微生物群的信号。在本章中,我们将评估肠道微生物群与EEC之间的相互作用及其对宿主生理的影响。我们将首先描述无菌动物中不同种群的EEC的变化。这种相互作用的介质,如微生物代谢物及其受体的作用也将被讨论。最后,将介绍利用宿主-微生物串扰进行治疗的不同策略,重点是肥胖和相关疾病。
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引用次数: 23
Treatment of Diabetes and Obesity by Rationally Designed Peptide Agonists Functioning at Multiple Metabolic Receptors. 合理设计多肽受体激动剂治疗糖尿病和肥胖症。
Pub Date : 2017-01-01 Epub Date: 2017-08-15 DOI: 10.1159/000475737
Noushafarin Khajavi, Heike Biebermann, Matthias Tschöp, Richard DiMarchi

Obesity and its comorbidities such as type 2 diabetes constitute major worldwide health threats, and the identification of an effective medical intervention has emerged as a global priority. The limited effectiveness of historical, anti-obesity treatments is commonly attributed to the complexity of the disease and the redundancy of metabolic regulatory mechanisms that sustain body weight. At the forefront of obesity research is the development of combinational drug therapies that simultaneously target multiple regulatory pathways, which promote dysfunctional metabolism. Recently, molecularly crafted unimolecular "multi-agonism" of balanced activity at 3 key receptors involved in metabolism and specifically the glucagon-like peptide (GLP)-1 receptor, glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon receptor was reported as superior to conventional monoagonist therapy. These mixed peptide agonists are designed to pharmacologically integrate the insulinotropic and anorexigenic effects of GLP-1, the thermogenic and lipolytic activities of glucagon, and the insulinotropic and insulin sensitizing properties of GIP. The molecular mechanism of these purposefully promiscuous ligands is not completely understood, however, recent studies in pancreatic beta cells point to the prospect of a complex signaling network that can magnify the signaling of multi-agonist ligands. The activation of this signalosome might explain the additional therapeutic benefit inherent to simultaneous cellular activation through multiple metabolic receptors.

肥胖及其合并症,如2型糖尿病,构成了全球主要的健康威胁,确定有效的医疗干预措施已成为全球的优先事项。历史上抗肥胖治疗的有限效果通常归因于疾病的复杂性和维持体重的代谢调节机制的冗余。肥胖研究的前沿是开发联合药物治疗,同时针对多种调节途径,促进功能失调的代谢。最近,据报道,分子制造的单分子“多激动剂”在参与代谢的3个关键受体,特别是胰高血糖素样肽(GLP)-1受体,葡萄糖依赖性胰岛素性多肽(GIP)受体和胰高血糖素受体的平衡活性上优于传统的单激动剂治疗。这些混合肽激动剂旨在药理学上整合GLP-1的促胰岛素和厌氧作用,胰高血糖素的产热和溶脂活性,以及GIP的促胰岛素和胰岛素增敏特性。这些有目的的混杂配体的分子机制尚不完全清楚,然而,最近在胰腺β细胞中的研究指出了一个复杂的信号网络的前景,该网络可以放大多激动剂配体的信号。这种信号体的激活可能解释了通过多种代谢受体同时激活细胞所固有的额外治疗益处。
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引用次数: 15
The Changing Concept of Gut Endocrinology. 肠道内分泌学概念的变化。
Pub Date : 2017-01-01 Epub Date: 2017-08-15 DOI: 10.1159/000475728
Jens F Rehfeld

Gastrointestinal hormones are released from enteroendocrine cells in the digestive tract. More than 30 hormone genes are expressed, which make the gut the largest endocrine organ in the body. At present, it is feasible to conceive the hormones under 5 headings: the structural homology groups most hormones into 9 families, each of which is assumed to originate from a single gene. Today's hormone gene often has multiple phenotypes due to alternative splicing, tandem organization or differentiated maturation of the prohormone. By these mechanisms, more than 100 different hormonal peptides are released from the gut. Gut hormones are also widely expressed in extraintestinal cells. These cells may release different fragments of the same prohormone due to cell-specific processing pathways. Moreover, endocrine cells, immune cells, neurons, myocytes, kidney cells, sperm cells and cancer cells secrete gut peptides in different ways, so the same peptide may act for instance as a hormone, a neurotransmitter, a cytokine, a growth factor or a fertility factor. The targets of gastrointestinal hormones are specific G-protein coupled receptors that are expressed in the cell membrane all over the body. Thus, each gut hormone constitutes a regulatory system operating in the whole organism.

胃肠道激素由消化道内的肠内分泌细胞释放。有30多种激素基因表达,使肠道成为人体最大的内分泌器官。目前,可以将激素分为5类:结构同源性将大多数激素分为9个家族,每个家族都被认为起源于单个基因。由于选择性剪接、串联组织或激素原的分化成熟,当今的激素基因通常具有多种表型。通过这些机制,100多种不同的激素肽从肠道中释放出来。肠道激素也广泛表达于肠外细胞。由于细胞特异性的加工途径,这些细胞可能释放相同激素原的不同片段。此外,内分泌细胞、免疫细胞、神经元、肌细胞、肾细胞、精子细胞和癌细胞以不同的方式分泌肠道肽,因此同样的肽可以作为激素、神经递质、细胞因子、生长因子或生育因子。胃肠道激素的作用靶点是在全身细胞膜上表达的特异性g蛋白偶联受体。因此,每一种肠道激素构成了一个在整个生物体中运作的调节系统。
{"title":"The Changing Concept of Gut Endocrinology.","authors":"Jens F Rehfeld","doi":"10.1159/000475728","DOIUrl":"https://doi.org/10.1159/000475728","url":null,"abstract":"<p><p>Gastrointestinal hormones are released from enteroendocrine cells in the digestive tract. More than 30 hormone genes are expressed, which make the gut the largest endocrine organ in the body. At present, it is feasible to conceive the hormones under 5 headings: the structural homology groups most hormones into 9 families, each of which is assumed to originate from a single gene. Today's hormone gene often has multiple phenotypes due to alternative splicing, tandem organization or differentiated maturation of the prohormone. By these mechanisms, more than 100 different hormonal peptides are released from the gut. Gut hormones are also widely expressed in extraintestinal cells. These cells may release different fragments of the same prohormone due to cell-specific processing pathways. Moreover, endocrine cells, immune cells, neurons, myocytes, kidney cells, sperm cells and cancer cells secrete gut peptides in different ways, so the same peptide may act for instance as a hormone, a neurotransmitter, a cytokine, a growth factor or a fertility factor. The targets of gastrointestinal hormones are specific G-protein coupled receptors that are expressed in the cell membrane all over the body. Thus, each gut hormone constitutes a regulatory system operating in the whole organism.</p>","PeriodicalId":72906,"journal":{"name":"Endocrine development","volume":"32 ","pages":"8-19"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000475728","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35375894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Incretins and Their Endocrine and Metabolic Functions. 肠促胰岛素及其内分泌和代谢功能。
Pub Date : 2017-01-01 Epub Date: 2017-08-15 DOI: 10.1159/000475730
Jochen Seufert

Incretins are hormones secreted into the blood stream from the gut mucosa in response to nutrient intake. They have been characterized based on their capacity to lower blood glucose levels. The more potent reduction of blood glucose coupled to a more intensive stimulation of insulin secretion, in response to oral glucose uptake, as compared to intravenous glucose infusion has further been termed the "incretin effect." As a prototype incretin hormone, the biology of glucagon-like peptide 1 (GLP-1) has been intensively studied. GLP-1 actions are mediated through cyclic adenosine monophosphate-coupled membrane receptors. Classical physiological effects involve stimulation of insulin secretion from pancreatic beta cells and reduction of glucagon secretion from pancreatic alpha cells, inhibition of gastric motility, and increase of satiety with reduced food uptake. The understanding of these metabolic functions has led to the notion that incretin hormones, and specifically GLP-1, would represent ideal antidiabetic treatment options. As native GLP-1 is degraded by dipeptidyl peptidase type 4 (DPP-4) within minutes, other pharmacological approaches to exploit GLP-1 actions for the treatment of type 2 diabetes have been developed. These include DPP-4 inhibitors as oral medications and GLP-1 receptor agonists (incretin mimetics) as peptide compounds to be injected.

肠促胰岛素是肠道黏膜分泌到血液中的激素,是对营养摄入的反应。它们的特点是具有降低血糖水平的能力。与静脉输注葡萄糖相比,口服葡萄糖摄取更有效地降低血糖,同时更强烈地刺激胰岛素分泌,这进一步被称为“肠促胰岛素效应”。胰高血糖素样肽1 (glucagon-like peptide 1, GLP-1)作为一种原型促肠促素激素,其生物学研究已经深入。GLP-1的作用是通过环腺苷单磷酸偶联膜受体介导的。经典的生理效应包括刺激胰腺β细胞分泌胰岛素,减少胰腺α细胞分泌胰高血糖素,抑制胃运动,减少食物摄取增加饱腹感。对这些代谢功能的理解导致了肠促胰岛素激素,特别是GLP-1,将代表理想的抗糖尿病治疗选择的概念。由于天然GLP-1可在几分钟内被二肽基肽酶4 (DPP-4)降解,因此开发了其他利用GLP-1作用治疗2型糖尿病的药理学方法。这些包括口服药物的DPP-4抑制剂和注射肽化合物GLP-1受体激动剂(肠促胰岛素模拟物)。
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引用次数: 4
Development and Anatomy of the Enteroendocrine System in Humans. 人类肠内分泌系统的发育和解剖。
Pub Date : 2017-01-01 Epub Date: 2017-08-15 DOI: 10.1159/000475729
Carsten Posovszky

The gastrointestinal (GI) tract exhibits an enormous surface area that consists mostly of absorptive enterocytes. Enteroendocrine cells (EECs) are found scattered along the GI tract between absorptive enterocytes and other secretory cells, and comprise around 1% of the epithelial cell population. Interestingly, they develop from the same crypt stem cell as the other absorptive or secretory cells of the gut. EECs differentiate along the crypt villus axis and are renewed every 4-6 days, and hence possess a high plasticity. They constitute the largest endocrine system in the human body by secreting multiple peptide hormones to control, for example, postprandial digestion, insulin homeostasis, food intake, and gut motility. For this purpose, most EECs exhibit luminal sensors that detect the GI tract content. Thereafter, they may act either in a classical endocrine fashion, or by paracrine effects on nearby neural and immune cells. This creates a pivotal role for EECs to influence the GI immune system and the enteric nervous system. In this chapter, the anatomical characteristics, development, differentiation and maturation of EECs are described, and their important biological potential illustrated as part of the gut interacting sensory system.

胃肠道具有巨大的表面积,主要由吸收性肠细胞组成。肠内分泌细胞(EECs)分布在胃肠道吸收性肠细胞和其他分泌性细胞之间,约占上皮细胞群的1%。有趣的是,它们和肠道的其他吸收或分泌细胞一样,是由相同的隐窝干细胞发育而来的。EECs沿隐窝绒毛轴分化,每4-6天更新一次,因此具有很高的可塑性。它们是人体最大的内分泌系统,通过分泌多种多肽激素来控制餐后消化、胰岛素稳态、食物摄入和肠道蠕动等。为此,大多数eec都具有检测胃肠道内容物的管腔传感器。此后,它们可能以经典的内分泌方式起作用,或通过旁分泌作用于附近的神经和免疫细胞。这为EECs影响胃肠道免疫系统和肠神经系统创造了关键作用。在本章中,介绍了EECs的解剖特征、发育、分化和成熟,并说明了它们作为肠道相互作用感觉系统的一部分的重要生物学潜力。
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引用次数: 4
Role of Incretin Hormones in Bowel Diseases. 肠促胰岛素激素在肠道疾病中的作用。
Pub Date : 2017-01-01 Epub Date: 2017-08-15 DOI: 10.1159/000475731
Tamara Zietek, Nadine Waldschmitt, Eva Rath

Enteroendocrine cells (EEC) have been studied extensively for their ability to regulate gastrointestinal motility and insulin release by secretion of peptide hormones. In particular, the L cell-derived incretin glucagon-like peptide 1 has gained enormous attention due to its insulinotropic action and relevance in the treatment of type 2 diabetes. Yet, accumulating data indicates a critical role for EEC and incretins in metabolic adaptation and in orchestrating immune responses beyond blood glucose control. EEC actively sense the lamina propria and luminal environment including the microbiota via receptors and transporters, subsequently mediating signals by secreting hormones and cytokines. Data indicate that immune cells and cytokine-mediated signaling impacts EEC numbers and function during infection and chronic inflammation of the gut, suggesting EEC not only to play a role in these pathologies but also being a target of inflammatory processes. This review presents data on the interrelation of incretins and inflammatory signaling. It focuses on the impact of intestinal inflammation, in particular inflammatory bowel disease, on EEC and the potential role of EEC and incretins in these pathologies. Furthermore, it highlights endoplasmic reticulum unfolded protein response, cytokines and the intestinal microbiota as possible targets of inflammatory and EEC signaling.

肠内分泌细胞(EEC)因其通过分泌肽激素调节胃肠运动和胰岛素释放的能力而被广泛研究。特别是,L细胞衍生的胰高血糖素样肽1由于其胰岛素促胰岛素作用和与2型糖尿病治疗的相关性而受到了极大的关注。然而,越来越多的数据表明,EEC和肠促胰岛素在代谢适应和协调血糖控制以外的免疫反应中发挥着关键作用。EEC通过受体和转运体主动感知固有层和腔内环境,包括微生物群,随后通过分泌激素和细胞因子介导信号。数据表明,在感染和肠道慢性炎症期间,免疫细胞和细胞因子介导的信号传导影响EEC的数量和功能,这表明EEC不仅在这些病理中发挥作用,而且是炎症过程的靶标。这篇综述介绍了肠促胰岛素和炎症信号相互关系的数据。它侧重于肠道炎症,特别是炎症性肠病,对EEC的影响以及EEC和肠促胰岛素在这些病理中的潜在作用。此外,它强调内质网未折叠蛋白反应,细胞因子和肠道微生物群是炎症和EEC信号传导的可能靶点。
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引用次数: 6
期刊
Endocrine development
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