Hyponatremia is a common electrolyte imbalance which often results from hormonal disregulation. The study aims to investigate whether the apelin hormone, which plays a role in regulating salt and water balance in the body, can be used to treat hyponatremia.
The study will involve healthy volunteers who will be given a medication that causes their bodies to retain water, thus inducing a temporary hyponatremia state. The researchers will measure the volunteers' blood and urine electrolyte levels to see how these are influenced by apelin administration. As comparison, the same measurements will be done in volunteers dosed with placebo instead of apelin.
The researchers believe that apelin may be able to help to correct hyponatremia by increasing urine output. If the study focused in the healthy volunteers population is successful, the investigators will assess the effect of apelin administration in patients with chronic hyponatremia.
The study's hypothesis is that intravenous apelin will increase urinary excretion and sodium levels in healthy participants with artificially induced hyponatremia.

开始日期2024-03-01

申办/合作机构

Universitätsspital Basel

NCT03449251 / Active, not recruiting临床2期IIT

A Series of Pilot Studies to Evaluate the Haemodynamic and Metabolic Effects of Apelin and Relaxin in Healthy Humans, Subjects With Increased Weight and Patients With Type 2 Diabetes Mellitus

Type two diabetes mellitus (T2DM) is a common, long term metabolic disorder characterised by hyperglycaemia (high blood glucose) resulting from insulin resistance and relative insulin insufficiency. The risk of developing insulin resistance and subsequently T2DM is increased by being overweight and also through a sedentary lifestyle. As the onset can be gradual, physiological damage may have occurred prior to diagnosis. Diabetes is associated with the development of microvascular complications (diabetic nephropathy, neuropathy, and retinopathy), and macrovascular complications (coronary artery disease, peripheral arterial disease, and stroke). While there are many treatments available for T2DM, these complications may still arise, leading to significant morbidity and mortality. There is therefore an urgent need to identify novel signalling pathways that may contribute to the development of diabetes related complications. The identification of these pathways may ultimately lead to the development of new therapies targeting better blood glucose control and preventing these subsequent complications.
Both animal and human studies have indicated that two endogenous peptides, apelin and relaxin both act as vasodilators in the human cardiovascular system and could also have beneficial action in T2DM. Therefore, we aim to carry out experimental medicine studies to test this hypothesis, and explore the signalling pathway in the human vascular system.

开始日期2018-03-28

申办/合作机构

Cambridge University Hospitals NHS Foundation Trust

[+3]

NCT02724566 / Completed临床1期IIT

Influence of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers

Preclinical studies have demonstrated in mouse models that (PYR1)-apelin-13 exerts a glucose-regulating action in vivo. The (PYR1)-apelin-13 effect on insulin sensitivity in healthy overweighed volunteers has been previously assessed in a phase I clinical trial (APELINS study; NCT02033473). The APELINS-2 clinical trial aims to expand the initial proof of concept to the population targeted by future innovative insulin-sensitizing therapies: patients living with type 2 diabetes.

开始日期2016-05-01

申办/合作机构

Société Francophone Du Diabete

100 项与爱帕琳肽相关的临床结果

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100 项与爱帕琳肽相关的转化医学

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100 项与爱帕琳肽相关的专利（医药）

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项与爱帕琳肽相关的文献（医药）

2024-12-01·Theriogenology

Expression of the apelin system in the porcine pituitary during the oestrous cycle and early pregnancy and the effect of apelin on LH and FSH secretion

Article

作者: Dobrzyn, Kamil ; Zaobidna, Ewa ; Kiezun, Marta ; Smolinska, Nina ; Kaminski, Tadeusz ; Kopij, Grzegorz ; Gudelska, Marlena ; Rytelewska, Edyta ; Kisielewska, Katarzyna ; Wasilewska, Barbara

Reproductive success requires considerable energy investment. Research has shown that some adipokines, i.e. the hormones produced in adipose tissue, affect reproductive functions by influencing all structures of the hypothalamic-pituitary-ovarian axis. Apelin is a recently identified member of the adipokine family. To the best of the authors' knowledge, this is the first study to investigate the gene and protein expression of the apelin system (the apelin hormone and the apelin receptor, APJ) in the anterior (AP) and posterior (PP) pituitary lobes of the domestic pig during different phases of the oestrous cycle (days 2 to 3, 10 to 12, 14 to 16, and 17 to 19) and in early pregnancy (days 10 to 11, 12 to 13, 15 to 16, and 27 to 28). It was also assumed that apelin participates in the regulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion and influences Akt, MAPK/Erk1/2, and AMPK signalling pathways in the AP during the oestrous cycle. Apelin, APJ mRNAs and proteins were detected in both pituitary lobes. Apelin was identified in gonadotropes, somatotropes, lactotropes, and thyrotropes. The study also revealed that apelin and APJ mRNA/protein levels fluctuate during the oestrous cycle and early gestation. Apelin affects basal, GnRH- and/or insulin-stimulated gonadotropin secretion in some phases of the cycle, as well as the phosphorylation of Akt, MAPK/Erk1/2, and AMPK proteins in AP cells. These findings suggest that apelin may be produced locally in the pituitary and that this gland is receptive to apelin's action. The study also suggest that apelin may influence female reproductive functions by controlling the release of LH and FSH from AP cells, and that it affects Akt, MAPK/Erk1/2, and AMPK signalling pathways.

2024-12-01·Molecular Biology Reports

Quercetin prevents kidney against diabetes mellitus (type 1) in rats by inhibiting TGF-β/apelin gene expression

Article

作者: Firouzeh, Gholampour ; Zeinab, Karimi ; Gholamreza, Daryabor ; Hossein, Ashraf

BACKGROUNDOne of the main causes of diabetic nephropathy is oxidative stress induced by hyperglycemia. Apelin inhibits insulin secretion. Besides, renal expression of TGF-β is increased in diabetes mellitus (DM). The preventive effect of quercetin (Q) against renal functional disorders and tissue damage developed by DM in rats was assessed.METHODSForty male Wistar rats were grouped into normal control (NC), normal + quercetin (NQ: quercetin, 50 mg/kg/day by gavage), diabetic control (DC: streptozotocin, 65 mg/kg, i.p.), diabetic + quercetin pretreatment (D + Qpre), and diabetic + quercetin post-treatment (D + Qpost). All samples (24-hour urine, plasma, pancreatic, and renal tissues) were obtained at the terminal of the experiment.RESULTSCompared to NC and NQ groups, DM ended in elevated plasma and glucose levels, decreased plasma insulin level, kidney dysfunction, augmented levels of malondialdehyde, decreased level of reduced glutathione, reduced enzymatic activities of superoxide dismutase and catalase, elevated gene expression levels of apelin and TGF-β, also renal and pancreatic histological damages. Quercetin administration diminished entire the changes. However, the measure of improvement in the D + Qpre group was higher than that of the D + Qpost group.CONCLUSIONQuercetin prevents renal dysfunction induced by DM, which might be related to the diminution of lipid peroxidation, strengthening of antioxidant systems, and prevention of the apelin/ TGF-β signaling pathway.

2024-11-01·Neuroscience Letters

Effects of Apelin-13 on auditory system in STZ-induced diabetic rats

Article

作者: Kılınç, Sevtap ; Eylül Aydemir, Berfin ; Arzu Yiğit, Ayşe ; Güneşer, Özgecan ; Ölçüoğlu, Rukiye ; Kilinç, Sevtap

AIMDamage to the auditory pathways is one of the complications of diabetes. The aim of this study was to investigate the potential therapeutic effects of apelin-13 in the auditory pathways of rats with experimentally induced diabetes by examining its effect on auditory brainstem responses, cochlear oxidative stress and inflammatory cytokines.METHODSThirty-two male Wistar albino rats were divided into four groups: sham control, diabetes, apelin and diabetes + apelin. A single dose of 45 mg/kg streptozotocin (STZ) was administered to induce diabetes. The apelin group received 50 µg/kg apelin-13 for seven days intraperitoneally (ip). At the end of the apelin and STZ applications auditory brainstem responses (ABR) was recorded. At the end of the experiment, cochlea was removed and biochemical analyzes were performed.RESULTSIn ABR recordings, the latencies of wave V in diabetic group were observed to be longer than those of the control, with the apelin treatment exhibiting a partial reversal of this situation, particularly at specific frequencies and intensity levels. Apelin treatment leads to a significant increase in total antioxidant status (TAS) and a reduction in total oxidant status (TOS) and oxidative stress index (OSI) in cochlea compared to diabetic groups. The levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL-1 beta) in cochlear tissue were found to be significantly reduced in the apelin-treated group compared to the diabetic group.CONCLUSIONApelin-13 may have a protective effect on the auditory system and may be proposed as a potential new therapeutic strategy for the management diabetic auditory impairment.

项与爱帕琳肽相关的新闻（医药）

2024-09-03

·PRNewswire

Vasa Therapeutics Announces Initiation of Phase 1 First-in-Human Clinical Trial of VS-041 for the Treatment of Heart Failure with Preserved Ejection Fraction

Vasa Therapeutics granted MHRA Clinical Trial Authorization (CTA) for VS-041 for the treatment of heart failure with preserved ejection fraction (HFpEF) Company's seed funding extended to $11M ENCINITAS, Calif. and WROCLAW, Poland, Sept. 3, 2024 /PRNewswire/ -- Vasa Therapeutics ("Vasa"), a clinical stage biopharmaceutical company developing novel therapies for cardiovascular and metabolic aging, announced today that the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) has granted clinical trial authorization (CTA) for Vasa to commence a Phase 1 first-in-human clinical trial to evaluate the safety, tolerability, and pharmacokinetics of its investigational drug VS-041 in healthy adult participants. VS-041 is an oral compound with a novel mechanism of action for the potential treatment of heart failure with preserved ejection fraction (HFpEF). "The MHRA's authorization marks a major step forward in our mission to develop VS-041 as a disease-modifying therapy for HFpEF," said Artur Plonowski, MD, PhD, Chief Executive Officer, Vasa Therapeutics. "There are currently no approved HFpEF treatments that improve structural properties of myocardium and provide durable clinical benefit. By inhibiting the release of endotrophin, a biomarker and mediator of fibrotic and inflammatory responses, VS-041 has the potential to become the first personalized approach in HFpEF management that could be used in patients with elevated levels of endotrophin who have a high risk of an unfavorable prognosis." The commencement of the Phase 1 trial of VS-041 coincides with an extension of the Company's seed funding, bringing the total round to $11 million. The financing was led by Orphinic Scientific SA with participation from i&i Biotech Fund I SCSp. Proceeds will support the clinical development of VS-041 and advancement of Vasa's preclinical programs. About HFpEF and endotrophin Heart failure is a serious condition that affects more than 64 million people worldwide.1 Approximately 6.7 million Americans have heart failure, which is expected to increase to over 8.5 million Americans by 2030.2 Nearly half of patients with heart failure have heart failure with preserved ejection fraction (HFpEF)3, and the prevalence of HFpEF is increasing.2,4 Approximately 75% of patients with HFpEF will die within five years of initial hospitalization, and 84% will be rehospitalized.2 Currently approved therapies for HFpEF provide clinical improvement but do not result in disease modification and durable improvement upon discontinuation of the treatment.5 Endotrophin, a collagen type VI–derived signaling peptide, has been linked to cardiac metabolic dysregulation, inflammation, and fibrosis. Baseline plasma endotrophin levels HFpEF patients were shown to be strongly and independently associated with increased risk of poor outcomes (deaths or heart failure rehospitalizations).6 About VS-041 VS-041 is an oral compound that was discovered and developed by Vasa for the potential treatment of HFpEF. VS-041 robustly reduces cardiac fibrosis and significantly improves diastolic heart functions in a preclinical HFpEF model. The compound also inhibits the release of endotrophin from primary human cardiac fibroblasts. In GLP toxicology studies, VS-041 demonstrated a highly favorable safety and tolerability profile. Preclinical development of VS-041 was co-funded by the European Regional Development Fund and the Polish National Centre for Research and Development (POIR.01.01.01-00-1210/19-01). About Vasa Therapeutics Vasa is a privately held biopharmaceutical company developing therapeutics that target pathophysiologies of cardiovascular and metabolic aging. In addition to VS-041, Vasa developed a cutting-edge platform for long-acting apelin for combination treatment with incretins in obesity, especially for patients at risk for skeletal muscle loss or cardiovascular disease. As a monotherapy, long-acting apelin agonists could also be beneficial in treating muscle atrophy, heart failure, chronic kidney disease, or peripheral artery disease. Vasa's preclinical pipeline also includes a best-in-class inhibitor of CamKIId for heart failure and life-threatening arrhythmias. For more information, please visit References: James et al. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Lancet 2018; 392: 1789–858. Bozkurt B, Ahmad T, Alexander KM, Baker WL, Bosak K, Breathett K, Fonarow GC, Heidenreich P, Ho JE, Hsich E, Ibrahim NE, Jones LM, Khan SS, Khazanie P, Koelling T, Krumholz HM, Khush KK, Lee C, Morris AA, Page RL 2nd, Pandey A, Piano MR, Stehlik J, Stevenson LW, Teerlink JR, Vaduganathan M, Ziaeian B; Writing Committee Members. Heart Failure Epidemiology and Outcomes Statistics: A Report of the Heart Failure Society of America. J Card Fail. 2023 Oct;29(10):1412-1451. doi: 10.1016/j.cardfail.2023.07.006. Epub 2023 Sep 26. PMID: 37797885; PMCID: PMC10864030. Dunlay SM, Roger VL, Weston SA, Jiang R, Redfield MM. Longitudinal changes in ejection fraction in heart failure patients with preserved and reduced ejection fraction. Circ Heart Fail. 2012 Nov;5(6):720-6. doi: 10.1161/CIRCHEARTFAILURE.111.966366. Epub 2012 Aug 30. PMID: 22936826; PMCID: PMC3661289. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128:e240-e327. Packer M, Butler J, Zeller C, Pocock SJ, Brueckmann M, Ferreira JP, Filippatos G, Usman MS, Zannad F, Anker SD. Blinded Withdrawal of Long-Term Randomized Treatment With Empagliflozin or Placebo in Patients With Heart Failure. Circulation. 2023 Sep 26;148(13):1011-1022. Chirinos JA, Zhao L, Reese-Petersen AL, Cohen JB, Genovese F, Richards AM, Doughty RN, Díez J, González A, Querejeta R, Zamani P, Nuñez J, Wang Z, Ebert C, Kammerhoff K, Maranville J, Basso M, Qian C, Rasmussen DGK, Schafer PH, SeifFert D, Karsdal MA, Gordon DA, Ramirez-Valle F, Cappola TP. Endotrophin, a Collagen VI Formation-Derived Peptide, in Heart Failure. NEJM Evid. 2022 Oct;1(10):10.1056 SOURCE Vasa Therapeutics

临床申请临床1期

2024-07-29

·PipelineReview

BioAge Announces First Patient Dosed in the STRIDES Phase 2 Clinical Trial Evaluating Azelaprag as a Novel Treatment for Obesity in Combination with Tirzepatide

Trial to evaluate weight loss efficacy of azelaprag, an oral small molecule apelin receptor agonist that mimics key biological effects of exercise STRIDES is being conducted in collaboration with Lilly’s Chorus clinical development organization Primary endpoint is weight loss at 24 weeks, with exploratory endpoints including body composition and physical activity RICHMOND, CA, USA I July 29, 2024 I BioAge Labs, Inc., (“BioAge”), a clinical-stage biopharmaceutical company developing therapeutic product candidates for metabolic diseases by targeting the biology of human aging, today announced that the first patient has been dosed in the STRIDES Phase 2 clinical trial evaluating BioAge’s lead product candidate azelaprag in combination with tirzepatide for the treatment of obesity in adults aged 55 and older. Azelaprag is an orally available small molecule agonist of the apelin receptor APJ. Apelin is an exercise-induced signaling molecule (exerkine) that acts on APJ to mediate many of the metabolic benefits of physical activity. In a Phase 1b clinical trial in healthy older volunteers on 10 days of bed rest, azelaprag was observed to improve muscle metabolism, decrease muscle atrophy, and preserve measures of resting energy expenditure and cardiorespiratory fitness ( link ). Azelaprag has been well tolerated in more than 240 subjects across seven Phase 1 clinical trials to date. In mouse models of obesity, the addition of azelaprag approximately doubled the weight loss achieved with incretin drugs (GLP-1 receptor agonists) while restoring healthy body composition and physical function ( link ). “We believe combining azelaprag, an exercise mimetic, with tirzepatide, a GLP-1/GIP receptor agonist that decreases food intake, could provide a powerful pharmacological parallel to the exercise and diet interventions that form the foundation of obesity management,” said Kristen Fortney, PhD, CEO and co-founder of BioAge. “The STRIDES trial aims to demonstrate that activating apelin signaling with azelaprag is a potent complementary mechanism that can deliver increased weight loss efficacy in patients on incretins. In addition, this trial will provide a direct read-through to azelaprag’s potential as an orally available small molecule to achieve efficacy on par with injectable weight loss drugs when combined with incretins in an all-oral regimen.” STRIDES is a randomized, double-blind, placebo-controlled Phase 2 clinical trial of azelaprag in combination with tirzepatide that will enroll approximately 220 obese individuals aged 55 years and older. The trial will evaluate the efficacy, safety, and tolerability of two oral doses of azelaprag (300 mg once or twice daily) in combination with tirzepatide (5 mg subcutaneous injection once weekly). The primary endpoint is mean percent change in body weight at 24 weeks. Additional exploratory endpoints include body composition, glycemic control, obesity-related biomarkers, and patient-reported outcomes related to health and quality of life. Top-line results are anticipated in the fourth quarter of 2025. STRIDES is being conducted in collaboration with Eli Lilly and Company’s (Lilly) Chorus clinical development organization. Lilly is providing tirzepatide for the trial ( link ). A second planned Phase 2 clinical trial will assess azelaprag in combination with semaglutide (Wegovy ® ) with initiation expected in the first half of 2025. Together, the trials will seek to support BioAge’s therapeutic goal of developing an all-oral combination product for obesity. About BioAge Labs BioAge is a clinical-stage biopharmaceutical company developing therapeutic product candidates for metabolic diseases, such as obesity, by targeting the biology of human aging. BioAge’s lead product candidate, azelaprag, is an orally available small molecule agonist of APJ that was observed to promote metabolism and prevent muscle atrophy on bed rest in a Phase 1b clinical trial. In mid-2024, BioAge initiated a Phase 2 trial of azelaprag in combination with tirzepatide for the treatment of obesity in older adults. Azelaprag has potential as an oral regimen to amplify weight loss and improve body composition in patients on obesity therapy with incretin drugs. BioAge is also developing orally available small molecule brain penetrant NLRP3 inhibitors for the treatment of diseases driven by neuroinflammation. BioAge’s preclinical programs, based on novel insights from the company’s discovery platform built on human longevity data, also address key pathways in metabolic aging. SOURCE: BioAge Labs

临床2期临床1期

2024-07-13

·生物探索

Nature丨印明柱团队解析肿瘤组织中的微脉管组成细胞

引言肿瘤的生长离不开周围血管提供的氧气与营养物质。2024年7月10日，重庆大学附属三峡医院印明柱教授团队利用单细胞测序技术捕获肿瘤组织中的微脉管组成细胞，阐释了肿瘤脉管系统的复杂形成过程。相关研究成果以Tumor vasculature at single-cell resolution为标题发表在Nature杂志。脉管系统在肿瘤微环境中扮演着关键角色，主要由内皮细胞（ endothelial cell，EC）和血管周围细胞（perivascular cell）构成。内皮细胞形成了单层细胞的内皮层（endothelium），覆盖所有血管和淋巴管，包括动脉、静脉、毛细血管以及淋巴毛细管。这些细胞在维持血管的正常功能和结构方面起着至关重要的作用。诱导血管生成是肿瘤重要的特征之一。结合多种单细胞拟时序分析与斑马鱼模型，研究人员证明了肿瘤诱导的血管生成从静脉样血管床出芽，逆血流方向生长，逐步与动脉样血管融合。血管尖端样细胞（tip cell）在感知微环境中缺氧水平与血管生长因子（VEGF）信号时，延伸伪足，并向外迁移，引导新生血管方向。其后，血管茎状细胞（stalk cell）增殖，延长血管出芽，形成新生血管管腔。随着新生血管的延长并向动脉端靠近，研究人员发现尖端样细胞与茎状细胞共同表现出细胞缺氧水平的缓解。且尖端细胞逐渐从高表达Apelin（由APLN基因编码）的表型转变为Notch信号活化状态；而茎状细胞则从趋化因子分泌型转变为血管稳定型。值得注意的是，基于TCGA泛肿瘤数据的反卷积分析显示出APLN+尖端细胞的浸润与多种癌症的进展以及不良预后密切相关。此外，在三组独立的贝伐珠单抗（bevacizumab，一种anti-VEGF抗体，用于抗血管生成治疗）联合治疗队列中，仅有APLN+尖端细胞在治疗前后的显示出明显差异，且治疗响应者往往在治疗前有着更高比例的APLN+尖端细胞的浸润，标志着此类细胞在未来抗血管生成疗法的伴随诊断中具有重要意义。淋巴管内皮细胞在肿瘤微环境中呈现出两条不同的分化谱系，其一表现为淋巴管生成（lymphangiogenesis），另一条表现为抗原呈递（Antigen presentation）。在淋巴管生成过程中，VEGF信号、缺氧与炎症环境扮演者重要的调控角色。有趣的是，研究人员发现抗原呈递型淋巴内皮细胞（apLEC）能够特异表达抗炎因子TSC22D3。TSC22D3不仅能够抑制NF-κB的核转运与DNA结合能力，还能够介导缺氧诱导因子HIF-1α的降解。这可能是与不同LEC分化谱系相关。此外，在TCGA的反卷积预后分析中，淋巴管生成途径往往与疾病进展、不良预后相关，而apLEC则可作为疾病的保护性因素。血管周围细胞主要分为周细胞（pericyte, PC）与平滑肌细胞（smooth muscle cell， SMC）。研究表明，在肿瘤组织中，周细胞相比平滑肌细胞不仅表现出数量的增多，而且显示出更高的细胞多样性。因此，研究人员对周细胞的表型进行更加细致的刻画，包括（1）血管舒张相关PC（vasodilation-associated PC, vdPC）；（2）脂质细胞样PC（adipocyte-like PC, adiPC）；（3）肌样PC（myoid-like PC, myoPC）；（4）基质产出样PC（matrix-producing PC, matPC）。值得注意的是，对PC静息状态的刻画表明，matPC在肿瘤微环境中表现出静息状态的活化，并伴有由氧化磷酸化向糖酵解代谢方式的转变。进一步刻画matPC的分化轨迹，研究人员识别到一种促血管生成相关的BASP1+ matPC，可调控内质网应激在此过程中起重要的调控功能。生存分析也表明BASP1+ matPC在多种肿瘤组织的浸润标志着疾病进展与不良预后。最后，研究人员还剖析了肿瘤脉管系统与微环境细胞的交互作用。结合空间转录组数据，新生血管不仅表现出塑造促血管生成环境的能力，而且还显示出免疫调节功能。总之，该研究构建了第一份肿瘤脉管系统全息细胞图谱，不仅为更好理解肿瘤血管生成的复杂过程提供了新的视角，还为开发新的抗血管生成治疗策略提供了重要的理论基础。参考文献 https://www.nature.com/articles/s41586-024-07698-1 责编|探索君排版|探索君文章来源|“BioArt” End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell综述

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适应症	最高研发状态	国家/地区	公司	日期
心血管疾病	临床2期	英国	AstraZeneca PLC	2018-03-28
2型糖尿病	临床2期	英国	AstraZeneca PLC	2018-03-28

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


EASD2015	N/A	-	-	Apelin	鏇夢鹽顧窪繭衊壓鏇廠(積壓構膚獵願顧鹽醖範) = Average frequency of NO hypothalamic release is significantly reduced following infusion of low-doses of apelin in the digestive tract (0,11 ± 0,003 Hz vs 0,12 ± 0,002 for control; P<0.001) 窪鹽廠積範齋淵選選願 (蓋鬱獵蓋製範襯夢鬱齋 ) 更多	-	2015-09-16
				apelin