Liver-enriched antimicrobial peptide 2(University of Copenhagen)(Liver-enriched antimicrobial peptide 2(University of Copenhagen))

概要

基本信息

药物类型

合成多肽

别名

靶点

GHSR x LEAP2

作用方式

拮抗剂、抑制剂

作用机制

GHSR拮抗剂(促生长激素释放激素受体拮抗剂)、LEAP2抑制剂(liver enriched antimicrobial peptide 2 inhibitors)

治疗领域

内分泌与代谢疾病

在研适应症

2型糖尿病

非在研适应症

肥胖

原研机构

University of Copenhagen

在研机构

University of Copenhagen

非在研机构

Gentofte Hospital

权益机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

Sequence Code 4739034

关联

5

项与 Liver-enriched antimicrobial peptide 2(University of Copenhagen) 相关的临床试验

NCT06845033

/ Not yet recruitingN/AIIT

Effects of Antagonizing the Ghrelin Receptor on Brain Food Cue Reactivity in Obesity

The naturally occurring peptide hormone liver-expressed antimicrobial peptide 2 (LEAP2) in an antagonist/inverse agonist towards the ghrelin receptor. Ghrelin administration has previously been shown to increase food cue reactivity in brain regions related to appetite and reward using functional MRI scans.
The aim of this clinical study is to investigate the effects of LEAP2 infusion on food cue reactivity in brain regions related to appetite and reward. Since LEAP2 is an antagonist/inverse agonist towards the ghrelin receptor we hypothesize, that LEAP2 infusion will decrease food cue reactivity in the above-mentioned regions compared to placebo infusion.
Participants with obesity (BMI 30-50 kg/m2) will be included and complete two experimental days with either LEAP2 or placebo infusion in a randomized crossover manner. On experimental days, participants will undergo a MRI scan with functional and anatomical modalities.
The study will attribute to gain a deeper understanding of the ghrelin system and its interaction with appetite regulation.

开始日期2025-05-01

申办/合作机构-

NCT05603598

/ Unknown statusN/AIIT

LEAP2 on Postprandial Glucose Metabolism and Food Intake in Obese Males

The study aims to delineate the effects of the naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP-2) on postprandial glucose metabolism and food intake in obese volunteers. The overall objective is to investigate the physiological importance of LEAP-2 in obese subjects.

开始日期2022-08-24

申办/合作机构-

NCT04897984

/ Completed早期临床1期IIT

The Kinetics of LEAP2 in Man

The study aims to investigate the kinetics of the naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP-2) in healthy volunteers. The overall objective is to investigate the physiological importance of LEAP-2 in healthy subjects.

开始日期2021-05-24

申办/合作机构

Gentofte Hospital

100 项与 Liver-enriched antimicrobial peptide 2(University of Copenhagen) 相关的临床结果

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100 项与 Liver-enriched antimicrobial peptide 2(University of Copenhagen) 相关的转化医学

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100 项与 Liver-enriched antimicrobial peptide 2(University of Copenhagen) 相关的专利（医药）

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41

项与 Liver-enriched antimicrobial peptide 2(University of Copenhagen) 相关的文献（医药）

2024-12-15·Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics

血清生长激素释放肽和肝脏表达抗菌肽-2与儿童特发性矮身材的相关性.

Article

作者: Song, Ya-Wen ; Liu, Qing ; Zhang, Wei-Chun ; Chen, Bo

目的: 探讨生长激素释放肽（ghrelin）和肝脏表达抗菌肽-2（liver-expressed antimicrobial peptide-2, LEAP-2）在特发性矮身材（idiopathic short stature, ISS）患儿体内的表达水平，为进一步认识矮小症的病因提供参考依据。方法: 前瞻性选取2021年12月—2023年10月于石河子大学第一附属医院就诊的46例ISS患儿（ISS组）和身高正常的46例健康儿童作为研究对象（对照组），比较两组儿童一般资料及血清ghrelin、LEAP-2表达水平，并运用受试者操作特征曲线（receiver operating characteristic curve, ROC曲线）评价两指标在ISS患儿中的预测价值。结果: ISS组血清ghrelin水平高于对照组，LEAP-2低于对照组，LEAP-2/ghrelin比值低于对照组，差异均有统计学意义（P<0.05）。多因素logistic回归分析显示，HtSDS、胰岛素样生长因子-1、ghrelin、LEAP-2、LEAP-2/ghrelin比值与ISS的发生独立相关（P<0.05）。ROC曲线分析显示，ghrelin、LEAP-2、ghrelin/LEAP-2比值及三者联合预测ISS的AUC均>0.8；ghrelin、LEAP-2、LEAP-2/ghrelin比值的最佳截断值分别为5 607 pg/mL、1 155 pg/mL、0.212。ISS患儿ghrelin与实际年龄、LEAP-2、LEAP-2/ghrelin比值呈负相关（P<0.05），与生长速率、生长激素峰值呈正相关（P<0.05）；LEAP-2与生长速率、生长激素峰值、ghrelin呈负相关（P<0.05），与实际年龄、LEAP-2/ghrelin比值呈正相关（P<0.05）。结论: ghrelin、LEAP-2与ISS发生相关，可为ISS患儿的诊断和病因分析提供参考依据。.

2024-11-01·Fish & Shellfish Immunology

Antibacterial activity of recombinant liver-expressed antimicrobial peptide-2 derived from olive flounder, Paralichthys olivaceus

Article

作者: Jeon, Yu-Jeong ; Kim, Yeo-Reum ; Im, Min-Hyuk ; Choi, Mi-Jin ; Byun, Jun-Hwan ; Lim, Han Kyu ; Kim, Jong-Myoung

Liver-expressed antimicrobial peptide-2 (LEAP-2) is a cysteine-rich peptide that plays a crucial role in the innate immune system of fish. To investigate the molecular function of LEAP-2 from olive flounder, Paralichthys olivaceus, we cloned the gene encoding LEAP-2 using PCR and expressed it in Escherichia coli. Analysis of LEAP-2 expression revealed predominant transcripts in the liver and lower levels in the intestine of olive flounder, whereas their expression levels in the liver and head kidney increased, during the initial stage of infection with the aquapathogenic bacterium Edwardsiella piscicida. Recombinant LEAP-2 (rOfLEAP-2) purified from E. coli exhibited antimicrobial activity, as demonstrated by the ultrasensitive radial diffusion assay, against both Gram-positive (Bacillus subtilis, Streptococcus parauberis, and Lactococcus garvieae) and Gram-negative (Vibrio harveyi and E. coli) bacteria, with minimum inhibitory concentrations ranging from 25 to 100 μg/mL depending on the species tested. The antibacterial activity of rOfLEAP-2 was attributed to its ability to disrupt bacterial membranes, validated by the N-phenylnaphthalen-1-amine uptake assays and scanning electron microscope analysis against E. coli, V. harveyi, B. subtilis, and L. garvieae treated with rOfLEAP-2. Furthermore, a synergistic enhancement of antibacterial activity was observed when rOfLEAP-2 was combined with ampicillin or synthetic LEAP-1 peptide, suggesting a distinct mechanism of action from those of other antimicrobial agents. These findings provide evidence for the antibacterial efficacy of LEAP-2 from olive flounder, highlighting its potential therapeutic application against pathogenic bacteria.

2024-09-18·Journal of Endocrinology

The GHSR1a antagonist LEAP2 regulates islet hormone release in a sex-specific manner

Article

作者: Sarkar, Debalina ; King, Aileen J F ; Gilon, Patrick ; Delishaj, Blerinda ; Dereli, Ayse S ; Patterson, Michael ; Bolton, Olivia ; Despontin, Chloe ; Hewawasam, Nirun ; Reeves, Sue ; Hauge-Evans, Astrid C ; Almutairi, Maha

LEAP2, a liver-derived antagonist for the ghrelin receptor, GHSR1a, counteracts the effects of ghrelin on appetite and energy balance. Less is known about its impact on blood glucose-regulating hormones from pancreatic islets. Here, we investigate whether acyl-ghrelin (AG) and LEAP2 regulate islet hormone release in a cell-type- and sex-specific manner. Hormone content from secretion experiments with isolated islets from male and female mice was measured by radioimmunoassay and mRNA expression by qPCR. LEAP2 enhanced insulin secretion in islets from males (P < 0.01) but not females (P > 0.2), whilst AG-stimulated somatostatin release was significantly reversed by LEAP2 in males (P < 0.001) but not females (P > 0.2). Glucagon release was not significantly affected by AG and LEAP2. Ghsr1a, Ghrelin, Leap2, Mrap2, Mboat4, and Sstr3 islet mRNA expression did not differ between sexes, whereas the SSTR3 antagonist MK4256 enhanced glucose-induced insulin secretion in islets from males only. In control male islets maintained without 17-beta oestradiol (E2), AG exerted an insulinostatic effect (P < 0.05), with a trend towards reversal by LEAP2 (P = 0.06). Both were abolished by 72 h E2 pre-treatment (10 nmol/L, P > 0.2). AG-stimulated somatostatin release was inhibited by LEAP2 from control (P < 0.001) but not E2-treated islets (P > 0.2). LEAP2 and AG did not modulate insulin secretion from MIN6 beta cells and Mrap2 was downregulated (P < 0.05) and Ghsr1a upregulated (P < 0.0001) in islets from Sst−/− mice. Our findings show that AG and LEAP2 regulate insulin and somatostatin release in an opposing and sex-dependent manner, which in males can be modulated by E2. We suggest that regulation of SST release is a key starting point for understanding the role of GHSR1a in islet function and glucose metabolism.

100 项与 Liver-enriched antimicrobial peptide 2(University of Copenhagen) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
2型糖尿病	临床1期	-	University of Copenhagen	-
肥胖	药物发现	丹麦	Gentofte Hospital	2020-11-17

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临床结果

适应症

分期

评价

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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


NCT05603598 (LEAP2, EASD2023)	N/A	肥胖	-	LEAP2 infusion	繭襯製願範選選醖廠簾(範鹽襯鹽鏇鏇願夢繭夢) = 選獵廠餘蓋鏇憲鏇遞鑰醖窪艱簾壓簾餘觸窪齋 (壓繭淵淵齋廠願繭製獵 ) 更多	积极	2023-10-04
				Placebo infusion	繭襯製願範選選醖廠簾(範鹽襯鹽鏇鏇願夢繭夢) = 淵鏇餘壓壓繭繭鬱膚觸醖窪艱簾壓簾餘觸窪齋 (壓繭淵淵齋廠願繭製獵 ) 更多
ADA2023	N/A	肥胖	-	LEAP2 infusion	(鬱蓋糧壓願醖網簾積網) = 遞窪遞憲鬱糧簾鹹膚鹽繭鹽觸蓋壓鬱鑰網構願 (構蓋築蓋築蓋選鏇顧獵 ) 更多	-	2023-06-20
				LEAP2 (Placebo infusion)	(鬱蓋糧壓願醖網簾積網) = 顧簾築襯繭積衊網築選繭鹽觸蓋壓鬱鑰網構願 (構蓋築蓋築蓋選鏇顧獵 ) 更多