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

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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序列信息

Sequence Code 4739034

关联

4

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

NCT05603598 / RecruitingN/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

NCT04621409 / Completed早期临床1期IIT

Effects of LEAP-2 on Postprandial Glucose Metabolism and Food Intake

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

开始日期2020-11-17

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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51

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

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 Edwadrsiella 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.

2024-07-23·Journal of Endocrinology

GHSR signalling in perinatal phases is involved in liver metabolism at puberty

Article

作者: Xavier, Carlos Henrique ; Matafome, Paulo ; Vanzela, Emerielle Cristine ; Cavalcante, Keilah Valéria Naves ; Ferreira-Junior, Marcos Divino ; Boschero, Antonio Carlos ; Gomes, Rodrigo Mello

Ghrelin has effects that range from the maturation of the central nervous system to the regulation of energy balance. The production of ghrelin increases significantly during the first weeks of life. Studies have addressed the metabolic effects of liver-expressed antimicrobial peptide 2 (LEAP2) in inhibiting the effects evoked by ghrelin, mainly in glucose homeostasis, insulin resistance, and lipid metabolism. Despite the known roles of ghrelin in the postnatal development, little is known about the long-term metabolic influences of modulation with the endogenous expressed growth hormone secretagogue receptor (GHSR) inverse agonist LEAP2. This study aimed to evaluate the contribution of GHSR signalling during perinatal phases, to neurodevelopment and energy metabolism in young animals, under inverse antagonism by LEAP2[1–14]. For this, two experimental models were used: (i) LEAP2[1–14] injections in female rats during the pregnancy. (ii) Postnatal modulation of GHSR with LEAP2[1–14] or MK677. Perinatal GHSR modulation by LEAP2[1–14] impacts glucose homeostasis in a sex and phase-dependent manner, despite no effects on body weight gain or food intake. Interestingly, liver PEPCK expression was remarkably impacted by LEAP2 injections. The observed results suggests that perinatal LEAP2 exposure can modulate liver metabolism and systemic glucose homeostasis. In addition, these results, although not expressive, may just be the beginning of the metabolic imbalance that will occur in adulthood.

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

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肥胖	临床3期	丹麦	Gentofte Hospital	2020-11-17
2型糖尿病	临床1期	-	University of Copenhagen	-

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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	鑰願憲窪構鏇鬱獵醖簾(蓋淵築餘鑰構糧鑰範糧) = 夢糧夢簾襯網鑰襯襯鑰鹹淵膚醖獵艱願製憲憲 (醖襯齋鹽餘鹹觸醖淵簾 ) 更多	积极	2023-10-04
				Placebo infusion	鑰願憲窪構鏇鬱獵醖簾(蓋淵築餘鑰構糧鑰範糧) = 蓋夢襯簾憲襯淵壓壓願鹹淵膚醖獵艱願製憲憲 (醖襯齋鹽餘鹹觸醖淵簾 ) 更多
ADA2023	N/A	肥胖	-	LEAP2 infusion	(顧壓願鹽觸憲衊範蓋襯) = 糧構襯繭構範鬱夢觸襯構齋襯夢獵糧網衊蓋顧 (壓淵觸窪鹽遞繭簾觸構 ) 更多	-	2023-06-20
				LEAP2 (Placebo infusion)	(顧壓願鹽觸憲衊範蓋襯) = 網廠窪鑰範廠淵觸製蓋構齋襯夢獵糧網衊蓋顧 (壓淵觸窪鹽遞繭簾觸構 ) 更多