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Valproic Acid Initiates Transdifferentiation of the Human Ductal Adenocarcinoma Cell-line Panc-1 Into α-Like Cells. 丙戊酸启动人导管腺癌细胞系Panc-1向α样细胞的转分化。
S. F. Petry, Naga Deepa Kandula, S. Günther, Christian S. M. Helker, U. Schagdarsurengin, T. Linn
Non-mesenchymal pancreatic cells are a potential source for cell replacement. Their transdifferentiation can be achieved by triggering epigenetic remodeling through e. g. post-translational modification of histones. Valproic acid, a branched-chain saturated fatty acid with histone deacetylase inhibitor activity, was linked to the expression of key transcription factors of pancreatic lineage in epithelial cells and insulin transcription. However, the potential of valproic acid to cause cellular reprogramming is not fully understood. To shed further light on it we employed next-generation RNA sequencing, real-time PCR, and protein analyses by ELISA and western blot, to assess the impact of valproic acid on transcriptome and function of Panc-1-cells. Our results indicate that valproic acid has a significant impact on the cell cycle, cell adhesion, histone H3 acetylation, and metabolic pathways as well as the initiation of epithelial-mesenchymal transition through acetylation of histone H3 resulting in α-cell-like characteristics. We conclude that human epithelial pancreatic cells can be transdifferentiated into cells with endocrine properties through epigenetic regulation by valproic acid favoring an α-cell-like phenotype.
非间充质胰腺细胞是细胞替代的潜在来源。它们的转分化可以通过触发表观遗传重塑来实现。组蛋白的翻译后修饰。丙戊酸是一种支链饱和脂肪酸,具有组蛋白去乙酰化酶抑制剂活性,与胰腺上皮细胞中关键转录因子的表达和胰岛素转录有关。然而,丙戊酸引起细胞重编程的潜力尚未完全了解。为了进一步阐明这一点,我们采用了下一代RNA测序、实时PCR、ELISA和western blot蛋白分析来评估丙戊酸对panc -1细胞转录组和功能的影响。我们的研究结果表明,丙戊酸对细胞周期、细胞粘附、组蛋白H3乙酰化和代谢途径有显著影响,并通过组蛋白H3乙酰化引发上皮-间质转化,从而产生α-细胞样特征。我们的结论是,人胰腺上皮细胞可以通过丙戊酸的表观遗传调控转化为具有内分泌特性的细胞,有利于α-细胞样表型。
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引用次数: 0
Definition, Classification and Diagnosis of Diabetes Mellitus. 糖尿病的定义、分类与诊断。
Erwin Schleicher, Christian Gerdes, A. Petersmann, D. Müller-Wieland, U. Müller, G. Freckmann, L. Heinemann, M. Nauck, R. Landgraf
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引用次数: 14
Diabetes and Fatty Liver. 糖尿病和脂肪肝。
N. Stefan, M. Roden
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引用次数: 0
Glucose Measurement and Control in Patients with Type 1 or Type 2 Diabetes. 1型或2型糖尿病患者的血糖测量和控制
Sandra Schlüter, D. Deiss, B. Gehr, K. Lange, S. von Sengbusch, A. Thomas, R. Ziegler, G. Freckmann
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引用次数: 2
Adjustment of Anti-Hyperglycaemic Agents During Bowel Preparation for Colonoscopy in Patients with Diabetes. 糖尿病患者结肠镜检查肠准备期间抗高血糖药物的调整。
K. Müssig, H. Adamek
OBJECTIVEDue to the growing diabetes pandemic, the number of colonoscopies performed in patients with diabetes is steadily rising. However, recommendations on adjustments of anti-hyperglycaemic agents (AHG) during bowel preparation for colonoscopy are limited.METHODSA total of nine articles were revealed on a PubMed search using the search terms "diabetes" and "colonoscopy", "sigmoidoscopy", "endoscopy", "endoscopic intervention", "endoscopic invasive diagnostics", "endoscopic surgery", or "diabetes care in the hospital" and manual screening of the references of the articles reporting on AHG adjustment during bowel preparation.RESULTSRegular glucose measurements and the opportunity to contact the diabetes team were commonly advised. Recommendations also agreed that all oral AHG and short-acting insulin should be omitted when patients are on clear fluids. Recent studies suggest discontinuation of sodium-glucose cotransporter-2 (SGLT2) inhibitors even three days before the colonoscopy. In contrast, recommendations differed regarding adjustment of basal insulin depending on diabetes type and time point in relation to the intervention.CONCLUSIONSWhile discontinuation of oral AHG and short-acting insulin during bowel preparation for colonoscopy is generally accepted, recommendations on the adaptation of basal insulin follow different approaches.
目的:随着糖尿病的流行,糖尿病患者结肠镜检查的数量正在稳步上升。然而,关于在结肠镜检查的肠道准备过程中调整抗高血糖药物(AHG)的建议是有限的。方法在PubMed检索“糖尿病”和“结肠镜检查”、“乙状结肠检查”、“内窥镜检查”、“内窥镜干预”、“内窥镜侵入性诊断”、“内窥镜手术”或“医院糖尿病护理”,并人工筛选报道肠准备期间AHG调整的文章的参考文献,共检索到9篇文章。结果通常建议定期进行血糖测量,并有机会与糖尿病小组联系。建议还一致认为,当患者服用透明液体时,应省略所有口服AHG和短效胰岛素。最近的研究建议在结肠镜检查前三天停用钠-葡萄糖共转运蛋白-2 (SGLT2)抑制剂。相反,根据与干预相关的糖尿病类型和时间点,关于调整基础胰岛素的建议有所不同。结论:虽然在结肠镜检查肠准备期间停用口服AHG和短效胰岛素是普遍接受的,但对基础胰岛素的适应建议有不同的途径。
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引用次数: 2
Family Structure is Associated with Mental Health and Attention Deficit (Hyperactivity) Disorders in Adolescents with Type 1 Diabetes. 家庭结构与1型糖尿病青少年心理健康和注意缺陷(多动)障碍相关
C. Baechle, A. Stahl-Pehe, K. Castillo, R. Holl, J. Rosenbauer
OBJECTIVETo analyze the cross-sectional associations of family structure with mental health and attention deficit (hyperactivity) disorders (AD(H)D) in 11- to 17-year-old adolescents with early-onset type 1 diabetes participating in one of three baseline surveys as part of an ongoing cohort study.METHODSParents (n=1,631) completed the Strengths and Difficulties Questionnaire to screen for their child's mental health and answered questions about their child's diagnosis of AD(H)D. Associations between mental health or AD(H)D and family structure were analyzed using multivariable logistic regression analyses adjusted for various personal and diabetes-related variables.RESULTSCompared to adolescents living with both parents, adolescents living with one parent and his/her partner had 2.35 (95% confidence interval 1.32; 4.21) higher odds of abnormal screening result and 2.08 (1.09; 3.95) higher odds of a borderline screening result while adolescents living with a single parent had 1.84 (1.07; 3.17)/1.08 (0.53; 2.21) higher odds of abnormal/borderline screening results. The odds ratios for diagnosed attention deficit (hyperactivity) disorder were 2.17 (0.98; 4.84) for adolescents living with one parent and his/her partner and 1.27 (0.54; 3.01) for those living with a single parent vs. both parents.CONCLUSIONSOur results indicate higher odds of mental health problems and AD(H)D in adolescents with type 1 diabetes who do not live with both parents; this finding was most pronounced in individuals living with one parent and his/her partner vs. both parents. Longitudinal studies are needed to verify our results and elucidate the underlying mechanisms.
目的:分析11- 17岁早发型1型糖尿病青少年患者的家庭结构与心理健康和注意缺陷(多动)障碍(AD(H)D)的横断面关联,这些患者参加了一项正在进行的队列研究的三项基线调查之一。方法1631名家长填写《优势与困难问卷》,对孩子进行心理健康筛查,并回答有关AD(H)D诊断的问题。心理健康或AD(H)D与家庭结构之间的关系采用多变量逻辑回归分析,调整了各种个人和糖尿病相关变量。结果与双亲共同生活的青少年相比,单亲及其伴侣共同生活的青少年的患病率为2.35(95%可信区间为1.32;4.21)筛查结果异常的几率高于2.08 (1.09;3.95),而单亲家庭的青少年的边缘筛查结果的几率为1.84 (1.07;3.17) / 1.08 (0.53;2.21)异常/边缘筛查结果的几率更高。诊断为注意缺陷(多动)障碍的优势比为2.17 (0.98;与父母一方及其伴侣生活的青少年为4.84,与父母一方及其伴侣生活的青少年为1.27 (0.54;3.01)单亲家庭与双亲家庭。结论不与父母双方共同生活的青少年1型糖尿病患者出现心理健康问题和AD(H)D的几率较高;这一发现在与父母一方和他/她的伴侣生活在一起的个体与父母双方生活在一起的个体中最为明显。需要进行纵向研究来验证我们的结果并阐明潜在的机制。
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引用次数: 0
Position Paper on Lipid Therapy in Patients with Diabetes Mellitus. 糖尿病患者脂质治疗的立场文件。
K. Parhofer, A. Birkenfeld, W. Krone, M. Lehrke, N. Marx, M. Merkel, K. Schütt, A. Zirlik, D. Müller-Wieland
Hypertension,
高血压
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引用次数: 0
Diabetes Mellitus and the Heart. 糖尿病与心脏。
K. Schütt, T. Forst, A. Birkenfeld, A. Zirlik, D. Müller-Wieland, N. Marx
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引用次数: 1
Dietary recommendations for persons with type 2 diabetes mellitus. 2型糖尿病患者的饮食建议。
T. Skurk, A. Bosy-Westphal, A. Grünerbel, S. Kabisch, W. Keuthage, P. Kronsbein, K. Müssig, A. Pfeiffer, M. Simon, A. Tombek, K. Weber, Diana Rubin
{"title":"Dietary recommendations for persons with type 2 diabetes mellitus.","authors":"T. Skurk, A. Bosy-Westphal, A. Grünerbel, S. Kabisch, W. Keuthage, P. Kronsbein, K. Müssig, A. Pfeiffer, M. Simon, A. Tombek, K. Weber, Diana Rubin","doi":"10.1055/a-1624-5095","DOIUrl":"https://doi.org/10.1055/a-1624-5095","url":null,"abstract":"","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82036944","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
What is the Role of Thyroid Hormone Receptor Alpha 2 (TRα2) in Human Physiology? 甲状腺激素受体α2 (TRα2)在人体生理中的作用是什么?
Sarah Paisdzior, Marc Schuelke, H. Krude
Thyroid hormone receptors are nuclear receptors that function as transcription factors and are regulated by thyroid hormones. To date, a number of variants and isoforms are known. This review focuses on the thyroid hormone receptor α (TRα), in particular TRα2, an isoform that arises from alternative splicing of the THRA mRNA transcript. Unlike the TRα1 isoform, which can bind T3, the TRα2 isoform lacks a ligand-binding domain but still binds to DNA thereby antagonizing the transcriptional activity of TRα1. Although a regulatory role has been proposed, the physiological function of this TRα2 antagonism is still unclear due to limited in vitro and mouse model data. Recently, the first patients with resistance to thyroid hormone due to mutations in THRA, the TRα encoding gene, affecting the antagonistic function of TRα2 were described, suggesting a significant role of this particular isoform in human physiology.
甲状腺激素受体是受甲状腺激素调控的核受体,具有转录因子的功能。迄今为止,已知的变体和异构体有很多。本文综述了甲状腺激素受体α (TRα),特别是TRα2,一种由THRA mRNA转录物选择性剪接产生的异构体。与TRα1异构体可以结合T3不同,TRα2异构体缺乏配体结合结构域,但仍然与DNA结合,从而拮抗TRα1的转录活性。虽然已经提出了一种调节作用,但由于体外和小鼠模型数据有限,这种TRα2拮抗剂的生理功能尚不清楚。最近,首次报道了由于TRα编码基因THRA突变影响TRα2拮抗功能而对甲状腺激素产生耐药性的患者,这表明这种特殊的亚型在人体生理中起着重要作用。
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引用次数: 4
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Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
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