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Harnessing the melanocortin system in the control of food intake and glucose homeostasis 利用黑色皮质素系统控制食物摄入和葡萄糖稳态
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-02 DOI: 10.1016/j.peptides.2024.171255
Patrick Swan , Brett Johnson , Carel W. le Roux , Alexander D. Miras

The central and peripheral melanocortin system, comprising of five receptors and their endogenous ligands, is responsible for a wide array of physiological functions such as skin pigmentation, sexual function and development, and inflammation. A growing body of both clinical and pre-clinical research is demonstrating the relevance of this system in metabolic health. Disruption of hypothalamic melanocortin signalling is the most common cause of monogenic obesity in humans. Setmelanotide, an FDA-approved analogue of alpha-melanocyte stimulating hormone (α-MSH) that functions by restoring central melanocortin signalling, has proven to be a potent pharmacological tool in the treatment of syndromic obesity. As the first effective therapy targeting the melanocortin system to treat metabolic disorders, its approval has sparked research to further harness the links between these melanocortin receptors and metabolic processes. Here, we outline the structure of the central and peripheral melanocortin system, discuss its critical role in the regulation of food intake, and review promising targets that may hold potential to treat metabolic disorders in humans.

中枢和外周黑皮质素系统由五种受体及其内源性配体组成,负责多种生理功能,如皮肤色素沉着、性功能和发育以及炎症。越来越多的临床和临床前研究表明,该系统与代谢健康息息相关。下丘脑黑皮质素信号的中断是导致人类单基因肥胖症的最常见原因。塞美拉诺肽是美国食品及药物管理局(FDA)批准的α-促黑素细胞激素(α-MSH)类似物,可通过恢复中枢黑皮质素信号发挥功能。作为第一种针对黑色素皮质素系统治疗代谢紊乱的有效疗法,它的批准引发了进一步利用这些黑色素皮质素受体与代谢过程之间联系的研究。在这里,我们将概述中枢和外周黑色素皮质素系统的结构,讨论它在调节食物摄入量中的关键作用,并回顾可能有望治疗人类代谢紊乱的靶点。
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引用次数: 0
NPYR modulation: Potential for the next major advance in obesity and type 2 diabetes management? NPYR 调节:肥胖症和 2 型糖尿病治疗的下一个重大进展的潜力?
IF 3 4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-31 DOI: 10.1016/j.peptides.2024.171256
Ryan A. Lafferty, Peter R. Flatt, Nigel Irwin

The approval of the glucagon-like peptide 1 (GLP-1) mimetics semaglutide and liraglutide for management of obesity, independent of type 2 diabetes (T2DM), has initiated a resurgence of interest in gut-hormone derived peptide therapies for the management of metabolic diseases, but side-effect profile is a concern for these medicines. However, the recent approval of tirzepatide for obesity and T2DM, a glucose-dependent insulinotropic polypeptide (GIP), GLP-1 receptor co-agonist peptide therapy, may provide a somewhat more tolerable option. Despite this, an increasing number of non-incretin alternative peptides are in development for obesity, and it stands to reason that other hormones will take to the limelight in the coming years, such as peptides from the neuropeptide Y family. This narrative review outlines the therapeutic promise of the neuropeptide Y family of peptides, comprising of the 36 amino acid polypeptides neuropeptide Y (NPY), peptide tyrosine-tyrosine (PYY) and pancreatic polypeptide (PP), as well as their derivatives. This family of peptides exerts a number of metabolically relevant effects such as appetite regulation and can influence pancreatic beta-cell survival. Although some of these actions still require full translation to the human setting, potential therapeutic application in obesity and type 2 diabetes is conceivable. However, like GLP-1 and GIP, the endogenous NPY, PYY and PP peptide forms are subject to rapid in vivo degradation and inactivation by the serine peptidase, dipeptidyl-peptidase 4 (DPP-4), and hence require structural modification to prolong circulating half-life. Numerous protective modification strategies are discussed in this regard herein, alongside related impact on biological activity profile and therapeutic promise.

胰高血糖素样肽 1(GLP-1)仿制药 semaglutide 和 liraglutide 被批准用于治疗肥胖症(不包括 2 型糖尿病 (T2DM)),这再次激发了人们对肠道激素衍生肽疗法治疗代谢性疾病的兴趣,但这些药物的副作用是一个令人担忧的问题。不过,最近批准用于治疗肥胖症和 T2DM 的替扎帕肽(一种葡萄糖依赖性促胰岛素多肽 (GIP)、GLP-1 受体共拮抗剂肽类疗法)可能提供了一种更容易耐受的选择。尽管如此,越来越多治疗肥胖症的非促胰岛素替代肽正在研发中,其他激素在未来几年也将成为焦点,如神经肽 Y 家族的肽类。本综述概述了神经肽 Y 家族多肽的治疗前景,包括 36 个氨基酸的多肽神经肽 Y(NPY)、肽酪氨酸-酪氨酸(PYY)和胰多肽(PP)及其衍生物。这一系列肽具有许多与新陈代谢相关的作用,如调节食欲,并能影响胰腺β细胞的存活。虽然其中一些作用仍需要完全转化到人体环境中,但在肥胖症和 2 型糖尿病方面的潜在治疗应用是可以想象的。然而,与 GLP-1 和 GIP 一样,内源性 NPY、PYY 和 PP 肽形式在体内会被丝氨酸肽酶、二肽基肽酶 4(DPP-4)快速降解和灭活,因此需要进行结构修饰以延长循环半衰期。本文就此讨论了许多保护性修饰策略,以及对生物活性概况和治疗前景的相关影响。
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引用次数: 0
Expression patterns and behavioral effects of conopressin and APGWamide in the nudibranch Berghia stephanieae 锥体加压素和 APGWamide 在裸鳃蛙中的表达模式和行为效应。
IF 3 4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-29 DOI: 10.1016/j.peptides.2024.171253
Cheyenne C. Tait , Meagan N. Olson , Kristina Nedeljkovic , Emily Kirchner , Paul S. Katz

The highly conserved oxytocin/vasopressin family of nonapeptides plays many roles across the animal kingdom, from osmoregulation to reproductive physiology. We investigated the expression patterns and pharmacological effects of the gastropod ortholog of this peptide, conopressin, along with another peptide involved in gastropod reproduction, APGWamide, in the nudibranch Berghia stephanieae. A brain transcriptome was used to identify and annotate the gene sequences for the peptides and one conopressin receptor. In-situ hybridization chain reaction showed that many neurons in the brain expressed these peptides. However, the peptide genes were co-expressed by only three neurons, which were in the right cerebral ganglion, the same side on which the reproductive organs are located. A conopressin receptor (BSCPR1) was expressed in a prominent population of APGWamide expressing neurons. Placing animals in a solution containing the APGWamide peptide caused minimal behavioral changes. However, exposure to conopressin reduced locomotion, increased gut contractions, and caused voiding at high concentration. The genes for these peptides and BSCPR1 were expressed in cells in the digestive system. BSCPR1 was also expressed by a line of neurons on the anterior portion of the radula and would be contacted during feeding. APGWamide-expressing neurons were found in the genital ganglion. All three genes expressed in cells on sensory appendages. These results are consistent with the conopressin playing a variety of roles in the brain and the body and being involved in both reproduction and digestion. This study sheds light on the function of this ancient nonapeptide in a new-to-neuroscience invertebrate species.

高度保守的催产素/血管加压素非肽家族在整个动物界扮演着从渗透调节到生殖生理的多种角色。我们研究了该肽的腹足类直向同源物--加压素以及另一种参与腹足类繁殖的肽--APGWamide在裸鳃蛙Berghia stephanieae中的表达模式和药理作用。利用脑转录组确定并注释了肽和一种加压素受体的基因序列。原位杂交连锁反应显示,大脑中的许多神经元都表达了这些肽。然而,只有三个神经元共同表达了多肽基因,它们位于右侧大脑神经节,也就是生殖器官所在的同一侧。在表达 APGWamide 的神经元群中,有一种 conopressin 受体(BSCPR1)得到了表达。将动物置于含有 APGWamide 肽的溶液中,其行为变化极小。然而,接触 conopressin 会减少运动,增加肠道收缩,并在高浓度时引起排尿。这些肽和 BSCPR1 的基因在消化系统细胞中表达。BSCPR1也在桡骨前部的一系神经元中表达,并会在进食时接触到。在生殖节中发现了表达 APGWamide 的神经元。所有三个基因都在感觉附属器上的细胞中表达。这些结果表明, conopressin 在大脑和身体中发挥着多种作用,并参与生殖和消化。这项研究揭示了这种古老的非肽类物质在神经科学新发现的无脊椎动物物种中的功能。
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引用次数: 0
Interaction of Angiotensin-(1−7) with kinins in the kidney circulation: Role of B1 receptors 肾循环中血管紧张素-(1-7)与激肽的σ相互作用:B1 受体的作用。
IF 3 4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-29 DOI: 10.1016/j.peptides.2024.171246
Elizabeth Pereira Mendes , Danielle Ianzer , Diogo Barros Peruchetti , Robson Augusto Souza Santos , Maria Aparecida Ribeiro Vieira

Changes in renal hemodynamics impact renal function during physiological and pathological conditions. In this context, renal vascular resistance (RVR) is regulated by components of the Renin-Angiotensin System (RAS) and the Kallikrein-Kinin System (KKS). However, the interaction between these vasoactive peptides on RVR is still poorly understood. Here, we studied the crosstalk between angiotensin-(1−7) and kinins on RVR. The right kidneys of Wistar rats were isolated and perfused in a closed-circuit system. The perfusion pressure and renal perfusate flow were continuously monitored. Ang-(1−7) (1.0–25.0 nM) caused a sustained, dose-dependent reduction of relative RVR (rRVR). This phenomenon was sensitive to 10 nM A-779, a specific Mas receptor (MasR) antagonist. Bradykinin (BK) promoted a sustained and transient reduction in rRVR at 1.25 nM and 125 nM, respectively. The transient effect was abolished by 4 μM des-Arg9-Leu8-bradykinin (DALBK), a specific kinin B1 receptor (B1R) antagonist. Accordingly, des-Arg9-bradykinin (DABK) 1 μM (a B1R agonist) increased rRVR. Interestingly, pre-perfusion of Ang-(1−7) changed the sustained reduction of rRVR triggered by 1.25 nM BK into a transient effect. On the other hand, pre-perfusion of Ang-(1−7) primed and potentiated the DABK response, this mechanism being sensitive to A-779 and DALBK. Binding studies performed with CHO cells stably transfected with MasR, B1R, and kinin B2 receptor (B2R) showed no direct interaction between Ang-(1−7) with B1R or B2R. In conclusion, our findings suggest that Ang-(1−7) differentially modulates kinin's effect on RVR in isolated rat kidneys. These results help to expand the current knowledge regarding the crosstalk between the RAS and KKS complex network in RVR.

在生理和病理条件下,肾血流动力学的变化会影响肾功能。在这种情况下,肾血管阻力(RVR)受肾素-血管紧张素系统(RAS)和Kallikrein-激肽系统(KKS)成分的调节。然而,人们对这些血管活性肽与 RVR 之间的相互作用仍然知之甚少。在此,我们研究了血管紧张素-(1-7)和激肽对 RVR 的相互影响。我们分离了 Wistar 大鼠的右肾,并在闭路系统中进行灌注。对灌注压力和肾灌注液流量进行连续监测。Ang-(1-7)(1.0-25.0nM)导致相对 RVR(rRVR)持续、剂量依赖性降低。这种现象对 10nM A-779 很敏感,A-779 是一种特异性 Mas 受体(MasR)拮抗剂。缓激肽(BK)分别在 1.25nM 和 125nM 时促进 rRVR 的持续和短暂降低。4μM des-Arg9-Leu8-缓激肽(DALBK)(一种特异性激肽 B1 受体(B1R)拮抗剂)可消除瞬时效应。相应地,1μM des-Arg9-缓激肽(DABK)(一种 B1R 激动剂)可增加 rRVR。有趣的是,预灌注 Ang-(1-7) 使 1.25nM BK 引发的 rRVR 持续降低转变为短暂效应。另一方面,Ang-(1-7)的预灌注启动并增强了 DABK 反应,这种机制对 A-779 和 DALBK 敏感。用稳定转染 MasR、B1R 和缓激肽 B2 受体的 CHO 细胞进行的结合研究表明,Ang-(1-7)与 B1R 或 B2R 之间没有直接相互作用。总之,我们的研究结果表明,在离体大鼠肾脏中,Ang-(1-7)可不同程度地调节激肽对 RVR 的影响。这些结果有助于扩展目前有关 RAS 和 KKS 复合物网络在 RVR 中相互影响的知识。
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引用次数: 0
Chronic exposure to incretin metabolites GLP-1(9−36) and GIP(3−42) affect islet morphology and beta cell health in high fat fed mice 长期暴露于增量素代谢物 GLP-1(9-36)和 GIP(3-42)会影响高脂喂养小鼠的胰岛形态和β细胞健康。
IF 3 4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-28 DOI: 10.1016/j.peptides.2024.171254
Ananyaa Sridhar, Dawood Khan, Gayathri Babu, Nigel Irwin, Victor A. Gault, Peter R. Flatt, Charlotte R. Moffett

The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are rapidly degraded by dipeptidyl peptidase-4 (DPP-4) to their major circulating metabolites GLP-1(9−36) and GIP(3−42). This study investigates the possible effects of these metabolites, and the equivalent exendin molecule Ex(9−39), on pancreatic islet morphology and constituent alpha and beta cells in high-fat diet (HFD) fed mice. Male Swiss TO-mice (6–8 weeks-old) were maintained on a HFD or normal diet (ND) for 4 months and then received twice-daily subcutaneous injections of GLP-1(9−36), GIP(3−42), Ex(9−39) (25 nmol/kg bw) or saline vehicle (0.9% (w/v) NaCl) over a 60-day period. Metabolic parameters were monitored and excised pancreatic tissues were used for immunohistochemical analysis. Body weight and assessed metabolic indices were not changed by peptide administration. GLP-1(9−36) significantly (p<0.001) increased islet density per mm2 tissue, that was decreased (p<0.05) by HFD. Islet, beta and alpha cell areas were increased (p<0.01) following HFD and subsequently reduced (p<0.01-p<0.001) by GIP(3−42) and Ex(9−39) treatment. While GLP-1(9−36) did not affect islet and beta cell areas in HFD mice, it significantly (p<0.01) decreased alpha cell area. Compared to ND and HFD mice, GIP(3−42) treatment significantly (p<0.05) increased beta cell proliferation. Whilst HFD increased (p<0.001) beta cell apoptosis, this was reduced (p<0.01-p<0.001) by both GLP-1(9−36) and GIP(3−42). These data indicate that the major circulating forms of GLP-1 and GIP, namely GLP-1(9−36) and GIP(3−42) previously considered largely inactive, may directly impact pancreatic morphology, with an important protective effect on beta cell health under conditions of beta cell stress.

增量激素--胰高血糖素样肽-1(GLP-1)和葡萄糖依赖性胰岛素促性多肽(GIP)会被二肽基肽酶-4(DPP-4)迅速降解为其主要的循环代谢产物 GLP-1(9-36) 和 GIP(3-42)。本研究调查了这些代谢物和等效的外显素分子 Ex(9-39) 对高脂饮食(HFD)喂养的小鼠的胰岛形态和组成α和β细胞可能产生的影响。雄性瑞士 TO 小鼠(6-8 周大)以高脂饮食或正常饮食(ND)饲养 4 个月,然后在 60 天内每天两次皮下注射 GLP-1(9-36)、GIP(3-42)、Ex(9-39) (25 nmol/kg bw) 或生理盐水载体(0.9% (w/v) NaCl)。对代谢参数进行监测,并对切除的胰腺组织进行免疫组化分析。服用多肽后,体重和评估的代谢指标没有变化。GLP-1(9-36)对胰腺组织的影响明显降低(p2)。
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引用次数: 0
Tirzepatide protects against doxorubicin-induced cardiotoxicity by inhibiting oxidative stress and inflammation via PI3K/Akt signaling 替扎帕肽通过 PI3K/Akt 信号转导抑制氧化应激和炎症,从而防止多柔比星诱发的心脏毒性
IF 3 4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-25 DOI: 10.1016/j.peptides.2024.171245
Ling Chen , Xi Chen , Bing Ruan , Hongjie Yang , Yang Yu

Background

Doxorubicin (DOX) is a highly effective and widely used cytotoxic agent with application for various malignancies, but it’s clinically limited due to its cardiotoxicity Oxidative stress and inflammation were reported to take part in DOX-induced cardiotoxicity. Tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist has been approved to treat type 2 diabetes. However, its role in DOX-induced cardiotoxicity and the underlying mechanisms has not been explored.

Methods

The cardioprotective properties of Tirzepatide against DOX-induced cardiotoxicity are examined in this work both in vivo and in vitro. For four weeks, an intraperitoneal injection of 4 mg/kg DOX was used to cause cardiotoxicity in C57BL/6 mice. To ascertain the cardioprotective function and underlying mechanisms of Tirzepatide against DOX-induced cardiotoxicity, mice and H9c2 cells were treated with and without Tirzepatide.

Results

Tirzepatide treatment significantly inhibited DOX-induced oxidative stress, inflammation and cardiac injury. Mechanistically, PI3K/Akt signaling pathway contributes to the protective effect of Tirzepatide against DOX-induced cardiotoxicity and inhibited PI3K/Akt signaling pathway with LY294002 almost blocked its therapeutic effect.

Conclusions

Collectively, Tirzepatide could alleviate DOX-induced oxidative stress, inflammation and cardiac injury via activating PI3K/Akt signaling pathway and Tirzepatide may be a novel therapeutic target for DOX-induced cardiotoxicity.

背景多柔比星(Doxorubicin,DOX)是一种高效且应用广泛的细胞毒性药物,可用于多种恶性肿瘤,但由于其心脏毒性,临床应用受到限制。替扎帕肽是一种胰高血糖素样肽-1(GLP-1)和葡萄糖依赖性促胰岛素多肽(GIP)双受体激动剂,已被批准用于治疗 2 型糖尿病。本研究在体内和体外研究了替哌肽对 DOX 引起的心脏毒性的保护作用。连续四周向 C57BL/6 小鼠腹腔注射 4 mg/kg DOX,使其产生心脏毒性。为了确定替扎帕肽对 DOX 引起的心脏毒性的心脏保护功能和潜在机制,小鼠和 H9c2 细胞分别接受了替扎帕肽治疗和未接受替扎帕肽治疗。从机理上讲,PI3K/Akt 信号通路是替哌肽对 DOX 引起的心脏毒性具有保护作用的原因,而用 LY294002 抑制 PI3K/Akt 信号通路几乎阻断了替哌肽的治疗作用。
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引用次数: 0
The impact of GLP-1 signalling on the energy metabolism of pancreatic islet β-cells and extrapancreatic tissues GLP-1 信号对胰岛β细胞和胰腺外组织能量代谢的影响
IF 3 4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-22 DOI: 10.1016/j.peptides.2024.171243
Leah A. Peart, Matthew Draper, Andrei I. Tarasov

Glucagon-like peptide-1 signalling impacts glucose homeostasis and appetite thereby indirectly affecting substrate availability at the whole-body level. The incretin canonically produces an insulinotropic effect, thereby lowering blood glucose levels by promoting the uptake and inhibiting the production of the sugar by peripheral tissues. Likewise, GLP-1 signalling within the central nervous system reduces the appetite and food intake, whereas its gastric effect delays the absorption of nutrients, thus improving glycaemic control and reducing the risk of postprandial hyperglycaemia. We review the molecular aspects of the GLP-1 signalling, focusing on its impact on intracellular energy metabolism. Whilst the incretin exerts its effects predominantly via a Gs receptor, which decodes the incretin signal into the elevation of intracellular cAMP levels, the downstream signalling cascades within the cell, acting on fast and slow timescales, resulting in an enhancement or an attenuation of glucose catabolism, respectively.

胰高血糖素样肽-1 信号影响葡萄糖稳态和食欲,从而间接影响全身的底物供应。增量素会产生促胰岛素效应,从而通过促进外周组织摄取和抑制糖的产生来降低血糖水平。同样,GLP-1 在中枢神经系统内的信号传导可降低食欲和食物摄入量,而其胃作用可延缓营养物质的吸收,从而改善血糖控制并降低餐后高血糖的风险。我们回顾了 GLP-1 信号的分子方面,重点是其对细胞内能量代谢的影响。增量蛋白主要通过 Gs 受体发挥其作用,Gs 受体将增量蛋白信号解码为细胞内 cAMP 水平的升高,细胞内的下游信号级联以快和慢的时间尺度发挥作用,分别导致葡萄糖分解代谢的增强或减弱。
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引用次数: 0
Gluco-metabolic response to exogenous oxytocin in totally pancreatectomized patients and healthy individuals 完全胰腺切除术患者和健康个体对体外催产素的糖代谢反应。
IF 3 4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-22 DOI: 10.1016/j.peptides.2024.171242
Vivian Kliim-Hansen , Ida M. Gether , Caroline T.-B. Juel , Anne-Marie Ellegaard , Miriam G. Pedersen , Bolette Hartmann , Nicolai J. Wewer Albrechtsen , Jens J. Holst , Asger B. Lund , Lærke S. Gasbjerg , Filip K. Knop

Oxytocin has been proposed to possess glucose-stabilizing effects through the release of insulin and glucagon from the pancreas. Also, exogenous oxytocin has been shown to stimulate extrapancreatic glucagon secretion in depancreatized dogs. Here, we investigated the effect of exogenous oxytocin on circulating levels of pancreatic and gut-derived glucose-stabilizing hormones (insulin [measured as C-peptide], glucagon, glucagon-like peptide 1 [GLP-1], and glucose-dependent insulinotropic polypeptide). We studied nine pancreatectomized (PX) patients and nine healthy controls (CTRLs) (matched on age and body mass index) before, during, and after an intravenous infusion of 10 IU of oxytocin administered over 12 min. Oxytocin did not increase plasma glucagon levels, nor induce any changes in plasma glucose, C-peptide, or GIP in any of the groups. Oxytocin decreased plasma glucagon levels by 19 ± 10 % in CTRLs (from 2.0 ± 0.5 [mean ± SEM] to 1.3 ± 0.2 pmol/l, P = 0.0025) and increased GLP-1 by 42 ± 22 % in PX patients (from 9.0 ± 1.0–12.7 ± 1.0 pmol/l, P = 0.0003). Fasting plasma glucose levels were higher in PX patients compared with CTRLs (13.1 ± 1.1 vs. 5.1 ± 0.1 mmol/l, P < 0.0001). In conclusion, the present findings do not support pancreas-mediated glucose-stabilizing effects of acute oxytocin administration in humans and warrant further investigation of oxytocin’s gluco-metabolic effects.

催产素被认为可通过从胰腺释放胰岛素和胰高血糖素来起到稳定血糖的作用。此外,外源性催产素还能刺激去势犬胰腺外胰高血糖素的分泌。在此,我们研究了外源性催产素对循环中胰腺和肠道来源的葡萄糖稳定激素(胰岛素 [以 C 肽衡量]、胰高血糖素、胰高血糖素样肽 1 [GLP-1] 和葡萄糖依赖性促胰岛素多肽)水平的影响。我们研究了九名胰腺切除术(PX)患者和九名健康对照组(CTRLs)(年龄和体重指数相匹配)在 12 分钟内静脉注射 10 IU 催产素之前、期间和之后的情况。催产素不会增加血浆胰高血糖素水平,也不会引起血浆葡萄糖、C 肽或 GIP 的任何变化。催产素使 CTRL 患者的血浆胰高血糖素水平降低了 19 ± 10%(从 2.0 ± 0.5 [mean ± SEM] 降至 1.3 ± 0.2 pmol/l,P = 0.0025),使 PX 患者的 GLP-1 水平升高了 42 ± 22%(从 9.0 ± 1.0 升至 12.7 ± 1.0 pmol/l,P = 0.0003)。与 CTRLs 相比,PX 患者的空腹血浆葡萄糖水平更高(13.1 ± 1.1 vs. 5.1 ± 0.1mmol/l,P < 0.0001)。总之,目前的研究结果并不支持人体急性注射催产素后胰腺介导的葡萄糖稳定作用,因此有必要进一步研究催产素的葡萄糖代谢作用。试验注册 ClinicalTrials.gov NCT02944110。
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引用次数: 0
Involvement of relaxin-family peptide-3 receptor (RXFP3) in the ventral dentate gyrus of the hippocampus in spatial and fear memory in rats 海马腹侧齿状回中的弛缓素家族肽-3受体(RXFP3)参与大鼠的空间记忆和恐惧记忆
IF 3 4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-22 DOI: 10.1016/j.peptides.2024.171244
Zohreh Vafaei , Fariba Khodagholi , Mohsen Nategh , Sara Nikseresht , Seyed Reza Hashemirad , Payman Raise-Abdullahi , Abbas Ali Vafaei , Fereshteh Motamedi

The neuropeptide relaxin-3 and its cognate receptor, relaxin family peptide-3 receptors (RXFP3), have been implicated in modulating learning and memory processes, but their specific roles remain unclear. This study utilized behavioral and molecular approaches to investigate the effects of putatively reversible blockade of RXFP3 in the ventral dentate gyrus (vDG) of the hippocampus on spatial and fear memory formation in rats. Male Wistar rats received bilateral vDG cannula implantation and injections of the RXFP3 antagonist, R3(BΔ23–27)R/I5 (400 ng/0.5 μL per side), or vehicle at specific time points before acquisition, consolidation, or retrieval phases of the Morris water maze and passive avoidance learning tasks. RXFP3 inhibition impaired acquisition in the passive avoidance task but not the spatial learning task. However, both memory consolidation and retrieval were disrupted in both tasks following RXFP3 antagonism. Ventral hippocampal levels of the consolidation-related kinase p70-S6 kinase (p70S6K) were reduced RXFP3 blockade. These findings highlight a key role for ventral hippocampal RXFP3 signaling in the acquisition, consolidation, and retrieval of spatial and emotional memories, extending previous work implicating this neuropeptide system in hippocampal memory processing.

神经肽松弛素-3及其同源受体松弛素家族肽-3受体(RXFP3)被认为与学习和记忆过程的调节有关,但它们的具体作用仍不清楚。本研究利用行为和分子方法研究了在海马腹侧齿状回(vDG)中可逆阻断 RXFP3 对大鼠空间记忆和恐惧记忆形成的影响。雄性 Wistar 大鼠在莫里斯水迷宫和被动回避学习任务的获得、巩固或检索阶段之前的特定时间点接受了双侧 vDG 插管植入和 RXFP3 拮抗剂 R3(BΔ23-27)R/I5 (每侧 400 ng/0.5 μL)或药物注射。抑制 RXFP3 会影响被动回避任务的获得,但不会影响空间学习任务。然而,在RXFP3拮抗后,这两项任务中的记忆巩固和检索都受到了干扰。RXFP3阻断后,巩固相关激酶p70-S6激酶(p70S6K)在海马腹侧的水平降低。这些发现突显了腹侧海马 RXFP3 信号在空间记忆和情感记忆的获得、巩固和检索中的关键作用,扩展了之前关于该神经肽系统与海马记忆处理有关的研究。
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引用次数: 0
Corrigendum to “Liraglutide inhibited AGEs induced coronary smooth muscle cell phenotypic transition through inhibiting the NF-κB signal pathway” [Peptides 112 (2019) 125–132] 更正:"利拉鲁肽通过抑制NF-κB信号通路抑制AGEs诱导的冠状动脉平滑肌细胞表型转变" [Peptides 112 (2019) 125-132]。
IF 3 4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-18 DOI: 10.1016/j.peptides.2024.171241
Beibing Di, Hong-Wei Li, Weiping Li, Bing Hua
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引用次数: 0
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Peptides
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