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Fasting and post prandial pancreatic and enteroendocrine hormone levels in obese and non-obese participants 肥胖者和非肥胖者的空腹和餐后胰腺和肠内分泌激素水平

IF 3 4区医学

Peptides Pub Date : 2024-03-13 DOI: 10.1016/j.peptides.2024.171186

Christopher A. Bannon , Claire L. Meek , Frank Reimann , Fiona M. Gribble

{"title":"Fasting and post prandial pancreatic and enteroendocrine hormone levels in obese and non-obese participants","authors":"Christopher A. Bannon , Claire L. Meek , Frank Reimann , Fiona M. Gribble","doi":"10.1016/j.peptides.2024.171186","DOIUrl":"https://doi.org/10.1016/j.peptides.2024.171186","url":null,"abstract":"<div><p>Circulating insulin levels are known to be increased in people with higher body mass index (BMI) due to effects of adiposity on insulin resistance, whilst gut hormones have a more complex relationship, with fasting peptideYY (PYY) reported to be inversely related to BMI. This study aimed to further explore fasting and post prandial pancreatic and gut hormone concentrations in plasma samples from obese and non-obese participants. Participants with healthy BMI (n=15), overweight BMI (n=29) and obesity (n=161) had samples taken fasting and 30 min post mixed liquid meal for analysis of glucagon-like peptide-1 (GLP-1), PYY, glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon. Data visualiation used linear discriminant analysis for dimensionality reduction, to visualise the data and assess scaling of each hormone. Fasting levels of insulin, GIP and PYY were shown to be key classifiers between the 3 groups on ANCOVA analysis, with an observation of increased GIP levels in overweight, but not obese participants. In non-obese subjects, fasting GIP, PYY and insulin correlated with BMI, whereas in subjects with obesity only the pancreatic hormones glucagon and insulin correlated with BMI. Concentrations of total GLP-1 in the fasting state correlated strongly with glucagon levels, highlighting potential assay cross-reactivities. The study, which included a relatively large number of subjects with severe obesity, supported previous evidence of BMI correlating negatively with fasting PYY and positively with fasting insulin. The observation of increased fasting GIP levels in overweight but not obese participants deserves further validation and mechanistic investigation.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"176 ","pages":"Article 171186"},"PeriodicalIF":3.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140135082","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}

引用次数: 0

The influence of insulin-induced hypoglycemia on copeptin concentrations 胰岛素诱导的低血糖对 copeptin 浓度的影响

IF 3 4区医学

Peptides Pub Date : 2024-03-09 DOI: 10.1016/j.peptides.2024.171185

Penelope Trimpou , Ioannis Bounias , Olof Ehn , Ola Hammarsten , Oskar Ragnarsson

{"title":"The influence of insulin-induced hypoglycemia on copeptin concentrations","authors":"Penelope Trimpou , Ioannis Bounias , Olof Ehn , Ola Hammarsten , Oskar Ragnarsson","doi":"10.1016/j.peptides.2024.171185","DOIUrl":"10.1016/j.peptides.2024.171185","url":null,"abstract":"<div><p>Plasma copeptin is a biomarker that reflects arginine vasopressin (AVP) secretion. In this study we measured copeptin during insulin tolerance test (ITT) in 65 patients referred to our department for evaluation of anterior pituitary function. Plasma for measurements of copeptin were collected at the start of the test and regurarly up to 120 minutes thereafter. Of 60 patients who developed significant hypoglycemia and were included in the analyses, 13 (22%) had corticotropic deficiency, 11 (18%) had thyreotropic deficiency, 33 (55%) had growth hormone deficiency and 4 (6%) had AVP deficieny (AVPD). Thirty-seven (62%) patients had at least one anterior pituitary deficiency. In patients without AVPD, median (range) copeptin increased from 4.5 pmol/L (1.3–33.0) to a maximum of 6.2 pmol/L (2.0–34.4; p<0.001). Baseline copeptin was similar in men and women, but maximal copeptin during ITT was higher in men. Copeptin concentrations were not affected by age, BMI, somatotropic, or corticotropic function. Copeptin concentrations were lower in patients with AVPD than patiets without AVPD, and in patients with thyrotropic deficiency, compared to patients with intact thyrotropic function, both at baseline and during ITT. In conclusion, copeptin increases significantly during insulin induced hypoglycemia but is of limited value in predicting anterior pituitary hormonal function.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"176 ","pages":"Article 171185"},"PeriodicalIF":3.0,"publicationDate":"2024-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140077020","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}

引用次数: 0

Characterization of rice endosperm-derived antidepressant-like peptide (REAP): An orally active novel tridecapeptide derived from rice protein 水稻胚乳抗抑郁样肽（REAP）的特征：一种从水稻蛋白中提取的具有口服活性的新型十三肽。

IF 3 4区医学

Peptides Pub Date : 2024-03-02 DOI: 10.1016/j.peptides.2024.171184

Saho Asakura , Kentaro Kaneko , Kohei Kawano , Maiko Shobako , Chendong Xu , Masaru Sato , Atsushi Kurabayashi , Hideyuki Suzuki , Akira Ito , Yuki Higuchi , Ryoko Nakayama , Hajime Takahashi , Kousaku Ohinata

{"title":"Characterization of rice endosperm-derived antidepressant-like peptide (REAP): An orally active novel tridecapeptide derived from rice protein","authors":"Saho Asakura , Kentaro Kaneko , Kohei Kawano , Maiko Shobako , Chendong Xu , Masaru Sato , Atsushi Kurabayashi , Hideyuki Suzuki , Akira Ito , Yuki Higuchi , Ryoko Nakayama , Hajime Takahashi , Kousaku Ohinata","doi":"10.1016/j.peptides.2024.171184","DOIUrl":"10.1016/j.peptides.2024.171184","url":null,"abstract":"<div><p>It is ideal to ingest bioactive substances from daily foods to stay healthy. Rice is the staple food for almost half of the human population. We found that an orally administered enzymatic digest of rice endosperm protein exhibits antidepressant-like effects in the tail suspension test (TST) using mice. A comprehensive peptide analysis of the digest using liquid chromatography-tandem mass spectrometry was performed, and a tridecapeptide QQFLPEGQSQSQK, detected in the digest, was chemosynthesized. Oral administration of the tridecapeptide exhibited antidepressant-like effects at a low dose comparable to classical antidepressant in the TST. This also exhibited anti-depressant-like effect in the forced swim test. We named it rice endosperm-derived antidepressant-like peptide (REAP). Intriguingly, intraperitoneal administration had no effect. Orally administered REAP(8−13) but not REAP(1−7) exhibited antidepressant-like activity, suggesting that the C-terminal structure is important for the antidepressant-like effect. We confirmed the presence of REAP, corresponding to rice glutelin type B4(130−142) and B5(130−142), in the digest. The effects of REAP were blocked by both dopamine D<sub>1</sub> and D<sub>2</sub> antagonists. These results suggest that it exerts its antidepressant-like activity through activation of the dopamine system.</p><p>Taken together, oral administration of a novel tridecapeptide exhibited antidepressant-like effects via the dopamine system. This is the first report of a rice-derived peptide that exhibits antidepressant-like effects.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"177 ","pages":"Article 171184"},"PeriodicalIF":3.0,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000378/pdfft?md5=09562522fb4e1022af519916dd6fdcfe&pid=1-s2.0-S0196978124000378-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022294","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}

引用次数: 0

Cathelicidin LL-37 promotes wound healing in diabetic mice by regulating TFEB-dependent autophagy 卡特里西丁 LL-37 通过调节 TFEB 依赖性自噬促进糖尿病小鼠的伤口愈合。

IF 3 4区医学

Peptides Pub Date : 2024-02-28 DOI: 10.1016/j.peptides.2024.171183

Liuqing Xi , Juan Du , Wen Xue , Kan Shao , Xiaohong Jiang , Wenfang Peng , Wenyi Li , Shan Huang

{"title":"Cathelicidin LL-37 promotes wound healing in diabetic mice by regulating TFEB-dependent autophagy","authors":"Liuqing Xi , Juan Du , Wen Xue , Kan Shao , Xiaohong Jiang , Wenfang Peng , Wenyi Li , Shan Huang","doi":"10.1016/j.peptides.2024.171183","DOIUrl":"10.1016/j.peptides.2024.171183","url":null,"abstract":"<div><p>Diabetic patients often experience impaired wound healing. Human cathelicidin LL-37 possesses various biological functions, such as anti-microbial, anti-inflammatory, and pro-wound healing activities. Autophagy has important effects on skin wound healing. However, little is known about whether LL-37 accelerates diabetic wound healing by regulating autophagy. In the study, we aimed to investigate the role of autophagy in LL-37-induced wound healing and uncover the underlying mechanisms involved. A full-thickness wound closure model was established in diabetic mice to evaluate the effects of LL-37 and an autophagy inhibitor (3-MA) on wound healing. The roles of LL-37 and 3-MA in regulating keratinocyte migration were assessed using transwell migration and wound healing assays. The activation of transcription factor EB (TFEB) was measured using western blotting and immunofluorescence (IF) assays of its nuclear translocation. The results showed that LL-37 treatment improved wound healing in diabetic mice, whereas these effects were reversed by 3-MA. <em>In vitro</em>, 3-MA decreased the effects of LL-37 on promoting HaCat keratinocyte migration in the presence of high glucose (HG). Mechanistically, LL-37 promoted TFEB activation and resulted in subsequent activation of autophagy, as evidenced by increased nuclear translocation of TFEB and increased expression of ATG5, ATG7, and beclin 1 (BECN1), whereas these changes were blocked by TFEB knockdown. As expected, TFEB knockdown damaged the effects of LL-37 on promoting keratinocyte migration. Collectively, these results suggest that LL-37 accelerates wound healing in diabetic mice by activating TFEB-dependent autophagy, providing new insights into the mechanism by which LL-37 promotes diabetic wound healing.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171183"},"PeriodicalIF":3.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996990","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}

引用次数: 0

The Mas agonist CGEN-856S prevents Ang II induced cardiomyocyte hypertrophy via nitric oxide production Mas 激动剂 CGEN-856S 可通过产生一氧化氮防止 Ang II 诱导的心肌细胞肥大。

IF 3 4区医学

Peptides Pub Date : 2024-02-28 DOI: 10.1016/j.peptides.2024.171182

Eduardo Nocchi , Sérgio Scalzo , Cibele Rocha-Resende , Pedro Almeida , Amanda Parreira , Kiany Miranda , Victor Moura , Robson A.S. dos Santos , Silvia Guatimosim

{"title":"The Mas agonist CGEN-856S prevents Ang II induced cardiomyocyte hypertrophy via nitric oxide production","authors":"Eduardo Nocchi , Sérgio Scalzo , Cibele Rocha-Resende , Pedro Almeida , Amanda Parreira , Kiany Miranda , Victor Moura , Robson A.S. dos Santos , Silvia Guatimosim","doi":"10.1016/j.peptides.2024.171182","DOIUrl":"10.1016/j.peptides.2024.171182","url":null,"abstract":"<div><p>With the previous knowledge of the cardioprotective effects of the Angiotensin-(1−7) axis, a agonist of Mas receptor has been described, the CGEN-856S. This peptide is more stable than Ang-(1−7), and has a low binding affinity to Angiotensin II receptors. Although the cardioprotective effects of CGEN-856S were previously shown <em>in vivo,</em> the mechanisms behind its effects are still unknown. Here, we employed a combination of molecular biology, confocal microscopy, and genetically modified mouse with Mas deletion to investigate the CGEN-856S protective signaling in cardiomyocytes. In isolated adult ventricular myocytes, CGEN-856S induced an increase in nitric oxide (NO) production which was absent in cells from Mas knockout mice. Using western blot, we observed a significant increase in phosphorylation of AKT after treatment with CGEN-856S. In addition, CGEN-856S prevented the Ang II induced hypertrophy and the nuclear translocation of GRK5 in a culture model of rat neonatal cardiomyocytes. Blockage of Mas receptor and inhibition of the NO synthase abolished the effects of CGEN-856S on Ang II treated cardiomyocytes. In conclusion, we show that CGEN-856S acting via receptor Mas induces NO raise to block Ang II induced cardiomyocyte hypertrophy. These results indicate that CGEN-856S acts very similarly to Ang-(1−7) in cardiac myocytes, highlighting its therapeutic potential for treating cardiovascular diseases.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171182"},"PeriodicalIF":3.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013126","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}

引用次数: 0

Intracerebroventricular administration of TRH Agonist, RX-77368 alleviates visceral pain induced by colorectal distension in rats 脑室内注射 TRH 激动剂 RX-77368 可减轻大鼠结肠直肠扩张引起的内脏疼痛

IF 3 4区医学

Peptides Pub Date : 2024-02-27 DOI: 10.1016/j.peptides.2024.171181

Muriel Larauche, Yong Sung Kim , Agata Mulak , Henri Duboc , Yvette Taché

{"title":"Intracerebroventricular administration of TRH Agonist, RX-77368 alleviates visceral pain induced by colorectal distension in rats","authors":"Muriel Larauche, Yong Sung Kim , Agata Mulak , Henri Duboc , Yvette Taché","doi":"10.1016/j.peptides.2024.171181","DOIUrl":"10.1016/j.peptides.2024.171181","url":null,"abstract":"<div><p>Thyrotropin-releasing hormone (TRH) acts centrally to exert pleiotropic actions independently from its endocrine function, including antinociceptive effects against somatic pain in rodents. Whether exogenous or endogenous activation of TRH signaling in the brain modulates visceral pain is unknown. Adult male Sprague-Dawley rats received an intracerebroventricular (ICV) injection of the stable TRH analog, RX-77368 (10, 30 and 100 ng/rat) or saline (5 µl) or were semi-restrained and exposed to cold (4°C) for 45 min. The visceromotor response (VMR) to graded phasic colorectal distensions (CRD) was monitored using non-invasive intracolonic pressure manometry. Naloxone (1 mg/kg) was injected subcutaneously 10 min before ICV RX-77368 or saline. Fecal pellet output was monitored for 1 h after ICV injection. RX-77368 ICV (10, 30 and 100 ng/rat) reduced significantly the VMR by 56.7%, 67.1% and 81.1% at 40 mmHg and by 30.3%, 58.9% and 87.4% at 60 mmHg respectively vs ICV saline. Naloxone reduced RX-77368 (30 and 100 ng, ICV) analgesic response by 51% and 28% at 40 mmHg and by 30% and 33% at 60 mmHg respectively, but had no effect per se. The visceral analgesia was mimicked by the acute exposure to cold. At the doses of 30 and 100 ng, ICV RX-77368 induced defecation within 30 min. These data established the antinociceptive action of RX-77368 injected ICV in a model of visceral pain induced by colonic distension through recruitment of both opioid and non-opioid dependent mechanisms.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171181"},"PeriodicalIF":3.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000342/pdfft?md5=58324a4a76471a875348aa9720a9cbfa&pid=1-s2.0-S0196978124000342-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996991","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}

引用次数: 0

Amphibian host-defense peptides with potential for Type 2 diabetes therapy – an updated review 具有治疗 2 型糖尿病潜力的两栖动物宿主防御肽--最新综述。

IF 3 4区医学

Peptides Pub Date : 2024-02-22 DOI: 10.1016/j.peptides.2024.171180

J. Michael Conlon, Bosede O. Owolabi, Peter R. Flatt, Yasser H.A. Abdel-Wahab

{"title":"Amphibian host-defense peptides with potential for Type 2 diabetes therapy – an updated review","authors":"J. Michael Conlon, Bosede O. Owolabi, Peter R. Flatt, Yasser H.A. Abdel-Wahab","doi":"10.1016/j.peptides.2024.171180","DOIUrl":"10.1016/j.peptides.2024.171180","url":null,"abstract":"<div><p>Investigations conducted since 2018 have identified several host-defense peptides present in frog skin secretions whose properties suggest the possibility of their development into a new class of agent for Type 2 diabetes (T2D) therapy. Studies <em>in vitro</em> have described peptides that (a) stimulate insulin release from BRIN-BD11 clonal β-cells and isolated mouse islets, (b) display β-cell proliferative activity and protect against cytokine-mediated apoptosis and (c) stimulate production of the anti-inflammatory cytokine IL-10 and inhibit production of the pro-inflammatory cytokines TNF-α and IL-1β. Rhinophrynin-27, phylloseptin-3.2TR and temporin F are peptides with therapeutic potential. Studies <em>in vivo</em> carried out in <em>db/db</em> and high fat-fed mice have shown that twice-daily administration of [S4K]CPF-AM1 and [A14K]PGLa-AM1, analogs of peptides first isolated from the octoploid frog <em>Xenopus amieti</em>, over 28 days lowers circulating glucose and HbA1c concentrations, increases insulin sensitivity and improves glucose tolerance and lipid profile. Peptide treatment produced potentially beneficial changes in the expression of skeletal muscle genes involved in insulin signaling and islet genes involved in insulin secretion in these murine models of T2D. Lead compounds uncovered by the study of frog HDPs may provide a basis for the design of new types of agents that can be used, alone or in combination with existing therapies, for the treatment of T2D.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171180"},"PeriodicalIF":3.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000330/pdfft?md5=a48b654362a742af45c89cc08e4d4406&pid=1-s2.0-S0196978124000330-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944287","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}

引用次数: 0

Adolescent social isolation disrupts developmental tuning of neuropeptide circuits in the hypothalamus to amygdala regulating social and defensive behavior 青少年的社会隔离会破坏下丘脑至杏仁核调节社会和防御行为的神经肽回路的发育调整

IF 3 4区医学

Peptides Pub Date : 2024-02-16 DOI: 10.1016/j.peptides.2024.171178

Hiroyuki Arakawa , Mana Tokashiki , Yuki Higuchi , Toshihiro Konno

{"title":"Adolescent social isolation disrupts developmental tuning of neuropeptide circuits in the hypothalamus to amygdala regulating social and defensive behavior","authors":"Hiroyuki Arakawa , Mana Tokashiki , Yuki Higuchi , Toshihiro Konno","doi":"10.1016/j.peptides.2024.171178","DOIUrl":"10.1016/j.peptides.2024.171178","url":null,"abstract":"<div><p>Engaging in positive social (i.e., prosocial) interactions during adolescence acts to modulate neural circuits that determine adult adaptive behavior. While accumulating evidence indicates that a strong craving for prosocial behavior contributes to sustaining neural development, the consequences of social deprivation during adolescence on social neural circuits, including those involving oxytocin (OXT) and vasopressin (AVP), are poorly characterized. We evaluated adaptive behaviors in socially isolated mice, including anxiety-like, social, and defensive behaviors, along with OXT and AVP neural profiles in relevant brain regions. Social isolation from postnatal day (P-)22 to P-48 induced enhanced defensive and exploratory behaviors, in nonsocial and social contexts. Unlike OXT neurons, AVP+ cell density in the paraventricular nucleus of the hypothalamus increases with age in males. Social isolation also modulated gene expression in the medial amygdala (MeA), including the upregulation of OXT receptors in males and the downregulation of AVP1a receptors in both sexes. Socially isolated mice showed an enhanced defensive, anogenital approach toward a novel adult female during direct social interactions. Subsequent c-Fos mapping revealed diminished neural activity in restricted brain areas, including the MeA, lateral septum, and posterior intralaminar nucleus of the thalamus, in socially isolated mice. These data indicate that neural signals arising from daily social interactions invoke region-specific modification of neuropeptide expression that coordinates with altered defensiveness and neural responsivities, including OXT- and AVP-projecting regions. The present findings indicate an involvement of OXT and AVP circuits in adolescent neural and behavioral plasticity that is tuned by daily social interaction.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171178"},"PeriodicalIF":3.0,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139773916","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}

引用次数: 0

GLP1R and GIPR expression and signaling in pancreatic alpha cells, beta cells and delta cells 胰腺α细胞、β细胞和δ细胞中 GLP1R 和 GIPR 的表达和信号传导。

IF 3 4区医学

Peptides Pub Date : 2024-02-14 DOI: 10.1016/j.peptides.2024.171179

Ali H. Shilleh , Katrina Viloria , Johannes Broichhagen , Jonathan E. Campbell , David J. Hodson

{"title":"GLP1R and GIPR expression and signaling in pancreatic alpha cells, beta cells and delta cells","authors":"Ali H. Shilleh , Katrina Viloria , Johannes Broichhagen , Jonathan E. Campbell , David J. Hodson","doi":"10.1016/j.peptides.2024.171179","DOIUrl":"10.1016/j.peptides.2024.171179","url":null,"abstract":"<div><p>Glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are transmembrane receptors involved in insulin, glucagon and somatostatin secretion from the pancreatic islet. Therapeutic targeting of GLP1R and GIPR restores blood glucose levels in part by influencing beta cell, alpha cell and delta cell function. Despite the importance of the incretin-mimetics for diabetes therapy, our understanding of GLP1R and GIPR expression patterns and signaling within the islet remain incomplete. Here, we present the evidence for GLP1R and GIPR expression in the major islet cell types, before addressing signaling pathway(s) engaged, as well as their influence on cell survival and function. While GLP1R is largely a beta cell-specific marker within the islet, GIPR is expressed in alpha cells, beta cells, and (possibly) delta cells. GLP1R and GIPR engage G<sub>s</sub>-coupled pathways in most settings, although the exact outcome on hormone release depends on paracrine communication and promiscuous signaling. Biased agonism away from beta-arrestin is an emerging concept for improving therapeutic efficacy, and is also relevant for GLP1R/GIPR dual agonism. Lastly, dual agonists exert multiple effects on islet function through GIPR > GLP1R imbalance, increased GLP1R surface expression and cAMP signaling, as well as beneficial alpha cell-beta cell-delta cell crosstalk.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171179"},"PeriodicalIF":3.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000329/pdfft?md5=6f72256f5ca9449c0e77674156c82450&pid=1-s2.0-S0196978124000329-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741681","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}

引用次数: 0

Studies on the in vitro mechanism and in vivo therapeutic effect of the antimicrobial peptide ACP5 against Trichophyton mentagrophytes 研究抗菌肽 ACP5 对脑毛癣菌的体外机制和体内疗效。

IF 3 4区医学

Peptides Pub Date : 2024-02-12 DOI: 10.1016/j.peptides.2024.171177

Kuiming Zou , Shaojie Zhang , Kedong Yin , Shiming Ren , Mengjun Zhang , Xiatong Li , Lixin Fan , Ruiling Zhang , Ruifang Li

{"title":"Studies on the in vitro mechanism and in vivo therapeutic effect of the antimicrobial peptide ACP5 against Trichophyton mentagrophytes","authors":"Kuiming Zou , Shaojie Zhang , Kedong Yin , Shiming Ren , Mengjun Zhang , Xiatong Li , Lixin Fan , Ruiling Zhang , Ruifang Li","doi":"10.1016/j.peptides.2024.171177","DOIUrl":"10.1016/j.peptides.2024.171177","url":null,"abstract":"<div><p><em>Trichophyton mentagrophytes</em> is a zoophilic dermatophyte that can cause dermatophytosis in humans and animals. Antimicrobial peptides (AMPs) are considered as a promising agent to overcome the drug-resistance of <em>T. mentagrophytes</em>. Our findings suggest that cationic antimicrobial peptide (ACP5) not only possesses stronger activity against <em>T. mentagrophytes</em> than fluconazole, but also shows lower toxicity to L929 mouse fibroblast cells than terbinafine. Notably, its resistance development rate after resistance induction was lower than terbinafine. The present study aimed to evaluate the fungicidal mechanism of ACP5 in vitro and its potential to treat dermatophyte infections in vivo. ACP5 at 1 ×MIC completely inhibited <em>T. mentagrophytes</em> spore germination in vitro. ACP5 severely disrupts the mycelial morphology, leading to mycelial rupture. Mechanistically, ACP5 induces excessive ROS production, damaging the integrity of the cell membrane and decreasing the mitochondrial membrane potential, causing irreversible damage in <em>T. mentagrophytes</em>. Furthermore, 1% ACP5 showed similar efficacy to the commercially available drug 1% terbinafine in a guinea pig dermatophytosis model, and the complete eradication of <em>T. mentagrophytes</em> from the skin by ACP5 was verified by tissue section observation. These results indicate that ACP5 is a promising candidate for the development of new agent to combat dermatophyte resistance.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"175 ","pages":"Article 171177"},"PeriodicalIF":3.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735814","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}

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