Peptides最新文献

{"title":"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","authors":"Ananyaa Sridhar,&nbsp;Dawood Khan,&nbsp;Gayathri Babu,&nbsp;Nigel Irwin,&nbsp;Victor A. Gault,&nbsp;Peter R. Flatt,&nbsp;Charlotte R. Moffett","doi":"10.1016/j.peptides.2024.171254","DOIUrl":"10.1016/j.peptides.2024.171254","url":null,"abstract":"<div><p>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&lt;0.001) increased islet density per mm² tissue, that was decreased (p&lt;0.05) by HFD. Islet, beta and alpha cell areas were increased (p&lt;0.01) following HFD and subsequently reduced (p&lt;0.01-p&lt;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&lt;0.01) decreased alpha cell area. Compared to ND and HFD mice, GIP(3−42) treatment significantly (p&lt;0.05) increased beta cell proliferation. Whilst HFD increased (p&lt;0.001) beta cell apoptosis, this was reduced (p&lt;0.01-p&lt;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.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"178 ","pages":"Article 171254"},"PeriodicalIF":3.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124001074/pdfft?md5=41a2f9cd81f9e54cf8646a0ad14d211d&pid=1-s2.0-S0196978124001074-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tirzepatide protects against doxorubicin-induced cardiotoxicity by inhibiting oxidative stress and inflammation via PI3K/Akt signaling","authors":"Ling Chen ,&nbsp;Xi Chen ,&nbsp;Bing Ruan ,&nbsp;Hongjie Yang ,&nbsp;Yang Yu","doi":"10.1016/j.peptides.2024.171245","DOIUrl":"10.1016/j.peptides.2024.171245","url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>The cardioprotective properties of Tirzepatide against DOX-induced cardiotoxicity are examined in this work both <em>in vivo</em> and <em>in vitro</em>. 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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusions</h3><p>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.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"178 ","pages":"Article 171245"},"PeriodicalIF":3.0,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141098441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of GLP-1 signalling on the energy metabolism of pancreatic islet β-cells and extrapancreatic tissues","authors":"Leah A. Peart,&nbsp;Matthew Draper,&nbsp;Andrei I. Tarasov","doi":"10.1016/j.peptides.2024.171243","DOIUrl":"https://doi.org/10.1016/j.peptides.2024.171243","url":null,"abstract":"<div><p>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 G_s 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.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"178 ","pages":"Article 171243"},"PeriodicalIF":3.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141084350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gluco-metabolic response to exogenous oxytocin in totally pancreatectomized patients and healthy individuals","authors":"Vivian Kliim-Hansen ,&nbsp;Ida M. Gether ,&nbsp;Caroline T.-B. Juel ,&nbsp;Anne-Marie Ellegaard ,&nbsp;Miriam G. Pedersen ,&nbsp;Bolette Hartmann ,&nbsp;Nicolai J. Wewer Albrechtsen ,&nbsp;Jens J. Holst ,&nbsp;Asger B. Lund ,&nbsp;Lærke S. Gasbjerg ,&nbsp;Filip K. Knop","doi":"10.1016/j.peptides.2024.171242","DOIUrl":"10.1016/j.peptides.2024.171242","url":null,"abstract":"<div><p>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, <em>P</em> = 0.0025) and increased GLP-1 by 42 ± 22 % in PX patients (from 9.0 ± 1.0–12.7 ± 1.0 pmol/l, <em>P</em> = 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, <em>P</em> &lt; 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.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"179 ","pages":"Article 171242"},"PeriodicalIF":3.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of relaxin-family peptide-3 receptor (RXFP3) in the ventral dentate gyrus of the hippocampus in spatial and fear memory in rats","authors":"Zohreh Vafaei ,&nbsp;Fariba Khodagholi ,&nbsp;Mohsen Nategh ,&nbsp;Sara Nikseresht ,&nbsp;Seyed Reza Hashemirad ,&nbsp;Payman Raise-Abdullahi ,&nbsp;Abbas Ali Vafaei ,&nbsp;Fereshteh Motamedi","doi":"10.1016/j.peptides.2024.171244","DOIUrl":"https://doi.org/10.1016/j.peptides.2024.171244","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"178 ","pages":"Article 171244"},"PeriodicalIF":3.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Liraglutide inhibited AGEs induced coronary smooth muscle cell phenotypic transition through inhibiting the NF-κB signal pathway” [Peptides 112 (2019) 125–132]","authors":"Beibing Di,&nbsp;Hong-Wei Li,&nbsp;Weiping Li,&nbsp;Bing Hua","doi":"10.1016/j.peptides.2024.171241","DOIUrl":"10.1016/j.peptides.2024.171241","url":null,"abstract":"","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"178 ","pages":"Article 171241"},"PeriodicalIF":3.0,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000949/pdfft?md5=c9b24767c8a823a64146be65b1d5d59f&pid=1-s2.0-S0196978124000949-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraperitoneal administration of arginine vasotocin (AVT) induces anorexigenic and anxiogenic actions via the brain V1a receptor-signaling pathway in the tiger puffer, Takifugu rubripes","authors":"Ryo Nagamine ,&nbsp;Norifumi Konno ,&nbsp;Tomoya Nakamachi ,&nbsp;Hajime Matsubara ,&nbsp;Kouhei Matsuda","doi":"10.1016/j.peptides.2024.171239","DOIUrl":"10.1016/j.peptides.2024.171239","url":null,"abstract":"<div><p>Arginine vasotocin (AVT) is produced mainly in the hypothalamus and as a neurohypophyseal hormone peripherally regulates water-mineral balance in sub-mammals. In addition, AVT-containing neurons innervate several areas of the brain, and AVT also acts centrally as both an anorexigenic and anxiogenic factor in goldfish. However, it is unclear whether these central effects operate in fish in general. In the present study, therefore, we investigated AVT-like immunoreactivity in the brain of the tiger puffer, a cultured fish with a high market value in Japan and also a representative marine teleost species, focusing particularly on whether AVT affects food intake and psychomotor activity. AVT-like immunoreactivity was distributed higher in the ventral region of the telencephalon, the hypothalamus and midbrain. Intraperitoneal (IP) administration of AVT at 100 pmol g⁻¹ body weight (BW) increased the immunoreactivity of phosphorylated ribosomal proteinS6 (RPS6), a neuronal activation marker, in the telencephalon and diencephalon, decreased food consumption and enhanced thigmotaxis. AVT-induced anorexigenic and anxiogenic actions were blocked by IP co-injection of a V1a receptor (V1aR) antagonist, Manning compound (MC) at 300 pmol g⁻¹ BW. These results suggest that AVT acts as an anorexigenic and anxiogenic factor via the V1aR-signaling pathway in the tiger puffer brain.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"178 ","pages":"Article 171239"},"PeriodicalIF":3.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucagon-like Peptide 1 Receptor Agonist use and the effect on diabetic retinopathy: An uncertain relationship","authors":"Benjamin T.K. Hui ,&nbsp;Jian Lee Yeong ,&nbsp;Tunde Peto ,&nbsp;Colin E. Willoughby","doi":"10.1016/j.peptides.2024.171240","DOIUrl":"10.1016/j.peptides.2024.171240","url":null,"abstract":"<div><p>Glucagon-like Peptide 1 Receptor Agonists (GLP-1 RAs) are a group of relatively novel medications for the treatment of diabetes mellitus. These medications can mimic the naturally occurring incretins of the body, which promote the release of insulin in response to hyperglycaemia. The anti-glycaemic effects of these medications can be profound and carry other metabolic benefits such as promoting weight loss. Clinical trials have shown GLP-1 RAs are safe to use from a cardiovascular perspective. However, some trials have suggested a link between GLP-1 RA use and worsening diabetic retinopathy. The conclusions surrounding this link are poorly established as data is drawn primarily from cardiovascular outcome trials. If an association does exist, a possible explanation might be the observed phenomenon of early worsening diabetic retinopathy with rapid correction of hyperglycaemic states. Trials which look at diabetic retinopathy as a primary outcome in relation to use of GLP-1 RAs are sparse and warrant investigation given the growing use of this group of medications. Therefore currently, it is uncertain what effect, beneficial or adverse, GLP-1 RA use has on diabetic retinopathy. This article provides an overview of GLP-1 RA use as a treatment for diabetes mellitus and the current understanding of their relationship with diabetic retinopathy.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"178 ","pages":"Article 171240"},"PeriodicalIF":3.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxytocin transported from the blood across the blood-brain barrier by receptor for advanced glycation end-products (RAGE) affects brain function related to social behavior","authors":"Haruhiro Higashida ,&nbsp;Yu Oshima ,&nbsp;Yasuhiko Yamamoto","doi":"10.1016/j.peptides.2024.171230","DOIUrl":"10.1016/j.peptides.2024.171230","url":null,"abstract":"<div><p>Oxytocin (OT) is a neuropeptide that primarily functions as a hormone controlling female reproductive processes. Since numerous recent studies have shown that single and repetitive administrations of OT increase trust, social interaction, and maternal behaviors in humans and animals, OT is considered a key molecule that regulates social memory and behavior. Furthermore, OT binds to receptors for advanced glycation end-products (RAGE), and it has been demonstrated that loss of RAGE in the brain vascular endothelial cells of mice fails to increase brain OT concentrations following peripheral OT administration. This leads to the hypothesis that RAGE is involved in the direct transport of OT, allowing it access to the brain by transporting it across the blood–brain barrier; however, this hypothesis is only based on limited evidence. Herein, we review the recent results related to this hypothesis, such as the mode of transport of OT in the blood circulation to the brain via different forms of RAGE, including membrane-bound full-length RAGE and soluble RAGE. We further review the modulation of brain function and social behavior, which seem to be mediated by RAGE-dependent OT. Overall, this review mostly confirms that RAGE enables the recruitment of circulating OT to the brain, thereby influencing social behavior. The requirement for further studies considering the physiological aspects of RAGE is also discussed.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"178 ","pages":"Article 171230"},"PeriodicalIF":3.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arginine vasopressin: Critical regulator of circadian homeostasis","authors":"Yoshiaki Yamaguchi","doi":"10.1016/j.peptides.2024.171229","DOIUrl":"https://doi.org/10.1016/j.peptides.2024.171229","url":null,"abstract":"<div><p>Circadian rhythms optimally regulate numerous physiological processes in an organism and synchronize them with the external environment. The suprachiasmatic nucleus (SCN), the center of the circadian clock in mammals, is composed of multiple cell types that form a network that provides the basis for the remarkable stability of the circadian clock. Among the neuropeptides expressed in the SCN, arginine vasopressin (AVP) has attracted much attention because of its deep involvement in the function of circadian rhythms, as elucidated in particular by studies using genetically engineered mice. This review briefly summarizes the current knowledge on the peptidergic distribution and topographic neuronal organization in the SCN, the molecular mechanisms of the clock genes, and the relationship between the SCN and peripheral clocks. With respect to the physiological roles of AVP and AVP-expressing neurons, in addition to a sex-dependent action of AVP in the SCN, studies using AVP receptor knockout mice and mice genetically manipulated to alter the clock properties of AVP neurons are summarized here, highlighting its importance in maintaining circadian homeostasis and its potential as a target for therapeutic interventions.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"177 ","pages":"Article 171229"},"PeriodicalIF":3.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}