Peptides最新文献_第7页

Positive interplay between FFAR4/GPR120, DPP-IV inhibition and GLP-1 in beta cell proliferation and glucose homeostasis in obese high fat fed mice FFAR4/GPR120、DPP-IV 抑制剂和 GLP-1 在肥胖高脂喂养小鼠β细胞增殖和葡萄糖稳态中的积极相互作用

IF 3 4区医学

Peptides Pub Date : 2024-04-14 DOI: 10.1016/j.peptides.2024.171218

A.I. Owolabi, R.C. Corbett, P.R. Flatt, A.M. McKillop

{"title":"Positive interplay between FFAR4/GPR120, DPP-IV inhibition and GLP-1 in beta cell proliferation and glucose homeostasis in obese high fat fed mice","authors":"A.I. Owolabi, R.C. Corbett, P.R. Flatt, A.M. McKillop","doi":"10.1016/j.peptides.2024.171218","DOIUrl":"10.1016/j.peptides.2024.171218","url":null,"abstract":"<div><p>G-protein coupled receptor-120 (GPR120; <em>FFAR4</em>) is a free fatty acid receptor, widely researched for its glucoregulatory and insulin release activities. This study aimed to investigate the metabolic advantage of FFAR4/GPR120 activation using combination therapy. C57BL/6 mice, fed a High Fat Diet (HFD) for 120 days to induce obesity-diabetes, were subsequently treated with a single daily oral dose of FFAR4/GPR120 agonist Compound A (CpdA) (0.1μmol/kg) alone or in combination with sitagliptin (50 mg/kg) for 21 days. After 21-days, glucose homeostasis, islet morphology, plasma hormones and lipids, tissue genes (qPCR) and protein expression (immunocytochemistry) were assessed. Oral administration of CpdA improved glucose tolerance (34% p<0.001) and increased circulating insulin (38% p<0.001). Addition of CpdA with the dipeptidyl peptidase-IV (DPP-IV) inhibitor, sitagliptin, further improved insulin release (44%) compared to sitagliptin alone and reduced fat mass (p<0.05). CpdA alone (50%) and in combination with sitagliptin (89%) induced marked reductions in LDL-cholesterol, with greater effects in combination (p<0.05). All treatment regimens restored pancreatic islet and beta-cell area and mass, complemented with significantly elevated beta-cell proliferation rates. A marked increase in circulating GLP-1 (53%) was observed, with further increases in combination (38%). With treatment, mice presented with increased <em>Gcg</em> (proglucagon) gene expression in the jejunum (130% increase) and ileum (120% increase), indicative of GLP-1 synthesis and secretion. These data highlight the therapeutic promise of FFAR4/GPR120 activation and the potential for combined benefit with incretin enhancing DPP-IV inhibitors in the regulation of beta cell proliferation and diabetes.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"177 ","pages":"Article 171218"},"PeriodicalIF":3.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000718/pdfft?md5=00b12a466d31f791dabd1fa8b9a1c076&pid=1-s2.0-S0196978124000718-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140708548","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

Glucagon-based therapy for people with diabetes and obesity: What is the sweet spot? 针对糖尿病和肥胖症患者的胰高血糖素疗法：甜蜜点在哪里？

IF 3 4区医学

Peptides Pub Date : 2024-04-13 DOI: 10.1016/j.peptides.2024.171219

Emma Rose McGlone , Tricia M.-M. Tan

{"title":"Glucagon-based therapy for people with diabetes and obesity: What is the sweet spot?","authors":"Emma Rose McGlone , Tricia M.-M. Tan","doi":"10.1016/j.peptides.2024.171219","DOIUrl":"https://doi.org/10.1016/j.peptides.2024.171219","url":null,"abstract":"<div><p>People with obesity and type 2 diabetes have a high prevalence of metabolic-associated steatotic liver disease, hyperlipidemia and cardiovascular disease. Glucagon increases hepatic glucose production; it also decreases hepatic fat accumulation, improves lipidemia and increases energy expenditure. Pharmaceutical strategies to antagonize the glucagon receptor improve glycemic outcomes in people with diabetes and obesity, but they increase hepatic steatosis and worsen dyslipidemia. Co-agonism of the glucagon and glucagon-like peptide-1 (GLP-1) receptors has emerged as a promising strategy to improve glycemia in people with diabetes and obesity. Addition of glucagon receptor agonism enhances weight loss, reduces liver fat and ameliorates dyslipidemia. Prior to clinical use, however, further studies are needed to investigate the safety and efficacy of glucagon and GLP-1 receptor co-agonists in people with diabetes and obesity and related conditions, with specific concerns regarding a higher prevalence of gastrointestinal side effects, loss of muscle mass and increases in heart rate. Furthermore, co-agonists with differing ratios of glucagon:GLP-1 receptor activity vary in their clinical effect; the optimum balance is yet to be identified.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"176 ","pages":"Article 171219"},"PeriodicalIF":3.0,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S019697812400072X/pdfft?md5=0655069d2d8f2cc91f7cd1e467464703&pid=1-s2.0-S019697812400072X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140558083","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

Negative association between basal oxytocin and oxytocin changes after repetitive transcranial magnetic stimulation in patients with treatment-resistant depression 耐药性抑郁症患者的基础催产素与重复经颅磁刺激后催产素变化之间存在负相关关系

IF 3 4区医学

Peptides Pub Date : 2024-04-13 DOI: 10.1016/j.peptides.2024.171217

Ryohei Kojima , Hiroshi Tateishi , Hiroko Kunitake , Yoshiomi Imamura , Yutaka Kunitake , Toru Murakawa , Chika Nagahama , Takumi Shiraishi , Ken Takada , Masataka Hirano , Airi Fukai , Akira Tomonari , Akira Monji , Yoshito Mizoguchi

{"title":"Negative association between basal oxytocin and oxytocin changes after repetitive transcranial magnetic stimulation in patients with treatment-resistant depression","authors":"Ryohei Kojima , Hiroshi Tateishi , Hiroko Kunitake , Yoshiomi Imamura , Yutaka Kunitake , Toru Murakawa , Chika Nagahama , Takumi Shiraishi , Ken Takada , Masataka Hirano , Airi Fukai , Akira Tomonari , Akira Monji , Yoshito Mizoguchi","doi":"10.1016/j.peptides.2024.171217","DOIUrl":"https://doi.org/10.1016/j.peptides.2024.171217","url":null,"abstract":"<div><p>Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulator effective for treating depressive symptoms in patients with treatment-resistant depression (TRD). One of the multiple mechanisms for its antidepressant effects proposed is related to the hypothalamus. Oxytocin is a neuropeptide synthesized in the hypothalamus that affects human behavior and psychology, including social and affiliative behaviors, stress regulation, and fear and emotion processing. There have been no reports on the relationship between rTMS and oxytocin for the treatment of TRD. Therefore, we aimed to investigate changes in salivary oxytocin concentrations in patients with TRD before and after 6 weeks of rTMS treatment. A total of 28 patients with TRD who received rTMS at Saga University Hospital between August 2013 and August 2020 were included. Although rTMS treatment significantly improved 24-item Hamilton Depression Rating Scale scores, rTMS treatment did not change mean salivary oxytocin after 6 weeks of treatment in patients with TRD. Multiple regression analysis revealed that the change in salivary oxytocin levels after rTMS treatment was negatively associated with basal oxytocin levels before rTMS treatment, suggesting that rTMS treatment tends to decrease oxytocin levels in patients with depression with high basal oxytocin levels while increasing them in those with low basal levels. These findings suggest that rTMS treatment improved depressive symptoms through mechanisms other than the modulatory effect on oxytocin levels in patients with TRD, while there is room for further studies to confirm these findings using a larger patient sample size and/or a sham rTMS procedure.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"177 ","pages":"Article 171217"},"PeriodicalIF":3.0,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140548953","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

Safety of native glucose-dependent insulinotropic polypeptide in humans 原生葡萄糖依赖性促胰岛素多肽对人体的安全性

IF 3 4区医学

Peptides Pub Date : 2024-04-12 DOI: 10.1016/j.peptides.2024.171214

Mads M. Helsted , Nina L. Schaltz , Lærke S. Gasbjerg , Mikkel B. Christensen , Tina Vilsbøll , Filip K. Knop

{"title":"Safety of native glucose-dependent insulinotropic polypeptide in humans","authors":"Mads M. Helsted , Nina L. Schaltz , Lærke S. Gasbjerg , Mikkel B. Christensen , Tina Vilsbøll , Filip K. Knop","doi":"10.1016/j.peptides.2024.171214","DOIUrl":"https://doi.org/10.1016/j.peptides.2024.171214","url":null,"abstract":"<div><p>In this systematic review, we assessed the safety and possible safety events of native glucose-dependent insulinotropic polypeptide (GIP)(1−42) in human studies with administration of synthetic human GIP. We searched the PubMed database for all trials investigating synthetic human GIP(1−42) administration. A total of 67 studies were included. Study duration ranged from 30 min to 6 days. In addition to healthy individuals, the studies included individuals with impaired glucose tolerance, type 2 diabetes, type 1 diabetes, chronic pancreatitis and secondary diabetes, latent autoimmune diabetes in adults, diabetes caused by a mutation in the hepatocyte nuclear factor 1-alpha gene, end-stage renal disease, chronic renal insufficiency, critical illness, hypoparathyroidism, or cystic fibrosis-related diabetes. Of the included studies, 78% did not mention safety events, 10% of the studies reported that no safety events were observed in relation to GIP administration, and 15% of the studies reported safety events in relation to GIP administration with most frequently reported event being a moderate and transient increased heart rate. Gastrointestinal safety events, and changes in blood pressure were also reported. Plasma concentration of active GIP(1−42) increased linearly with dose independent of participant phenotype. There was no significant correlation between achieved maximal concentration of GIP(1−42) and reported safety events. Clearance rates of GIP(1−42) were similar between participant groups. In conclusion, the available data indicate that GIP(1−42) in short-term (up to 6 days) infusion studies is generally well-tolerated. The long-term safety of continuous GIP(1−42) administration is unknown.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"177 ","pages":"Article 171214"},"PeriodicalIF":3.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140618609","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

Newly identified peptide Nigrocin-OA27 inhibits UVB induced melanin production via the MITF/TYR pathway 新发现的肽 Nigrocin-OA27 通过 MITF/TYR 途径抑制紫外线诱导的黑色素生成

IF 3 4区医学

Peptides Pub Date : 2024-04-11 DOI: 10.1016/j.peptides.2024.171215

Jiayi Li , Saige Yin , Ziqi Wei , Zhaoxun Xiao , Zijian Kang , Yutong Wu , Yubing Huang , Qiuye Jia , Ying Peng , Zeqiong Ru , Xiaohan Sun , Yuliu Yang , Qian Yang , Junyuan Wang , Chengxing Liu , Meifeng Yang , Ying Wang , Xinwang Yang

{"title":"Newly identified peptide Nigrocin-OA27 inhibits UVB induced melanin production via the MITF/TYR pathway","authors":"Jiayi Li , Saige Yin , Ziqi Wei , Zhaoxun Xiao , Zijian Kang , Yutong Wu , Yubing Huang , Qiuye Jia , Ying Peng , Zeqiong Ru , Xiaohan Sun , Yuliu Yang , Qian Yang , Junyuan Wang , Chengxing Liu , Meifeng Yang , Ying Wang , Xinwang Yang","doi":"10.1016/j.peptides.2024.171215","DOIUrl":"https://doi.org/10.1016/j.peptides.2024.171215","url":null,"abstract":"<div><p>Melasma is a common skin disease induced by an increase in the content of melanin in the skin, which also causes serious physical and mental harm to patients. In this research, a novel peptide (Nigrocin-OA27) from <em>Odorrana andersonii</em> is shown to exert a whitening effect on C57 mice pigmentation model. The peptide also demonstrated non-toxic and antioxidant capacity, and can significantly reduce melanin content in B16 cells. Topical application effectively delivered Nigrocin-OA27 to skin's epidermal and dermal layers and exhibited significant preventive and whitening effects on the UVB-induced ear pigmentation model in C57 mice. The whitening mechanism of Nigrocin-OA27 may be related to reduced levels of the microphthalmia-associated transcription factor and the key enzyme for melanogenesis-tyrosinase (TYR). Nigrocin-OA27 also inhibited the catalytic activity by adhering to the active core of TYR, thereby reducing melanin formation and deposition. In conclusion, Nigrocin-OA27 may be a potentially effective external agent to treat melasma by inhibiting aberrant skin melanin synthesis.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"177 ","pages":"Article 171215"},"PeriodicalIF":3.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140558516","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

Glucagon does not directly stimulate pituitary secretion of ACTH, GH or copeptin 胰高血糖素不会直接刺激垂体分泌促肾上腺皮质激素、促肾上腺皮质激素或促肾上腺皮质激素

IF 3 4区医学

Peptides Pub Date : 2024-04-10 DOI: 10.1016/j.peptides.2024.171213

Ida Stangerup , Sasha A.S. Kjeldsen , Michael M. Richter , Nicole J. Jensen , Jørgen Rungby , Steen Bendix Haugaard , Birgitte Georg , Jens Hannibal , Kjeld Møllgård , Nicolai J. Wewer Albrechtsen , Camilla Bjørnbak Holst

{"title":"Glucagon does not directly stimulate pituitary secretion of ACTH, GH or copeptin","authors":"Ida Stangerup , Sasha A.S. Kjeldsen , Michael M. Richter , Nicole J. Jensen , Jørgen Rungby , Steen Bendix Haugaard , Birgitte Georg , Jens Hannibal , Kjeld Møllgård , Nicolai J. Wewer Albrechtsen , Camilla Bjørnbak Holst","doi":"10.1016/j.peptides.2024.171213","DOIUrl":"https://doi.org/10.1016/j.peptides.2024.171213","url":null,"abstract":"<div><p>Glucagon is best known for its contribution to glucose regulation through activation of the glucagon receptor (GCGR), primarily located in the liver. However, glucagon’s impact on other organs may also contribute to its potent effects in health and disease. Given that glucagon-based medicine is entering the arena of anti-obesity drugs, elucidating extrahepatic actions of glucagon are of increased importance. It has been reported that glucagon may stimulate secretion of arginine-vasopressin (AVP)/copeptin, growth hormone (GH) and adrenocorticotrophic hormone (ACTH) from the pituitary gland. Nevertheless, the mechanisms and whether GCGR is present in human pituitary are unknown. In this study we found that intravenous administration of 0.2 mg glucagon to 14 healthy subjects was not associated with increases in plasma concentrations of copeptin, GH, ACTH or cortisol over a 120-min period. GCGR immunoreactivity was present in the anterior pituitary but not in cells containing GH or ACTH. Collectively, glucagon may not directly stimulate secretion of GH, ACTH or AVP/copeptin in humans but may instead be involved in yet unidentified pituitary functions.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"176 ","pages":"Article 171213"},"PeriodicalIF":3.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000664/pdfft?md5=0aa7ad2a846d81bd5b6470625fb4aadd&pid=1-s2.0-S0196978124000664-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140551244","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

GIP-derived GIP receptor antagonists – a review of their role in GIP receptor pharmacology 源自 GIP 的 GIP 受体拮抗剂--回顾其在 GIP 受体药理学中的作用

IF 3 4区医学

Peptides Pub Date : 2024-04-10 DOI: 10.1016/j.peptides.2024.171212

Mette Marie Rosenkilde, Peter Lindquist, Hüsün Sheyma Kizilkaya, Lærke Smidt Gasbjerg

{"title":"GIP-derived GIP receptor antagonists – a review of their role in GIP receptor pharmacology","authors":"Mette Marie Rosenkilde, Peter Lindquist, Hüsün Sheyma Kizilkaya, Lærke Smidt Gasbjerg","doi":"10.1016/j.peptides.2024.171212","DOIUrl":"https://doi.org/10.1016/j.peptides.2024.171212","url":null,"abstract":"<div><p>Surprisingly, agonists, as well as antagonists of the glucose-dependent insulinotropic polypeptide receptor (GIPR), are currently being used or investigated as treatment options for type 2 diabetes and obesity – and both, when combined with glucagon-like peptide 1 receptor (GLP-1R) agonism, enhance GLP-1-induced glycemia and weight loss further. This paradox raises several questions regarding not only the mechanisms of actions of GIP but also the processes engaged during the activation of both the GIP and GLP-1 receptors. Here, we provide an overview of studies of the properties and actions of peptide-derived GIPR antagonists, focusing on GIP(3-30)NH<sub>2</sub>, a naturally occurring N- and C-terminal truncation of GIP(1−42). GIP(3−30)NH<sub>2</sub> was the first GIPR antagonist administered to humans. GIP(3−30)NH<sub>2</sub> and a few additional antagonists, like Pro3-GIP, have been used in both <em>in vitro</em> and <em>in vivo</em> studies to elucidate the molecular and cellular consequences of GIPR inhibition, desensitization, and internalization and, at a larger scale, the role of the GIP system in health and disease. We provide an overview of these studies combined with recent knowledge regarding the effects of naturally occurring variants of the GIPR system and species differences within the GIP system to enhance our understanding of the GIPR as a drug target.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"177 ","pages":"Article 171212"},"PeriodicalIF":3.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000652/pdfft?md5=8a2cdb94cc49569fca843137558fabd2&pid=1-s2.0-S0196978124000652-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140620651","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

Identification and utility exploration of a highly potent and long-acting bullfrog GLP-1 analogue in GLP-1 and amylin combination therapy 一种强效长效牛蛙 GLP-1 类似物在 GLP-1 和淀粉样蛋白联合疗法中的鉴定和实用性探索

IF 3 4区医学

Peptides Pub Date : 2024-04-04 DOI: 10.1016/j.peptides.2024.171203

Xiao Sun , Dawei Yang , Yan Li , Jingjing Shi , Xiaolong Zhang , Tingzhuang Yi

{"title":"Identification and utility exploration of a highly potent and long-acting bullfrog GLP-1 analogue in GLP-1 and amylin combination therapy","authors":"Xiao Sun , Dawei Yang , Yan Li , Jingjing Shi , Xiaolong Zhang , Tingzhuang Yi","doi":"10.1016/j.peptides.2024.171203","DOIUrl":"https://doi.org/10.1016/j.peptides.2024.171203","url":null,"abstract":"<div><p>This study assesses the efficacy of an innovative therapeutic approach that combines GLP-1 and amylin analogues for weight reduction. Focusing on GLP-1 analogues from bullfrog (<em>Rana catesbeiana</em>), we designed ten bGLP-1 analogues with various modifications. Among them, bGLP-10 showed high potency in binding and activating GLP-1 receptors, with superior albumin affinity. In diet-induced obesity (DIO) mice fed a high-fat diet, bGLP-10 demonstrated significant superiority over semaglutide in reducing blood sugar and food intake at a dose of 10 nmol/kg (P < 0.001). Notably, in a chronic study involving DIO mice, the combination of bGLP-10 with the amylin analogue cagrilintide led to a more substantial weight loss (-38.4%, P < 0.001) compared to either the semaglutide-cagrilintide combination (-23.0%) or cagrilintide (-5.7%), bGLP-10 (-16.1%), and semaglutide (-10.9%) alone. Furthermore, the bGLP-10 and cagrilintide combination exhibited superior glucose control and liver lipid management compared to the semaglutide-cagrilintide combination (P < 0.001). These results highlight bGLP-10’s potential in GLP-1 and amylin-based therapies and suggest exploring more GLP-1 analogues from natural sources for anti-obesity and anti-diabetic treatments.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"177 ","pages":"Article 171203"},"PeriodicalIF":3.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140537069","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

Targeting the GLP-2 receptor in the management of obesity 靶向 GLP-2 受体治疗肥胖症

IF 3 4区医学

Peptides Pub Date : 2024-04-03 DOI: 10.1016/j.peptides.2024.171210

Thorir G. Pálsson , Hannah Gilliam-Vigh , Benjamin A.H. Jensen , Palle B. Jeppesen , Asger B. Lund , Filip K. Knop , Casper K. Nielsen

{"title":"Targeting the GLP-2 receptor in the management of obesity","authors":"Thorir G. Pálsson , Hannah Gilliam-Vigh , Benjamin A.H. Jensen , Palle B. Jeppesen , Asger B. Lund , Filip K. Knop , Casper K. Nielsen","doi":"10.1016/j.peptides.2024.171210","DOIUrl":"https://doi.org/10.1016/j.peptides.2024.171210","url":null,"abstract":"<div><p>Recent advancements in understanding glucagon-like peptide 2 (GLP-2) biology and pharmacology have sparked interest in targeting the GLP-2 receptor (GLP-2R) in the treatment of obesity. GLP-2 is a proglucagon-derived 33-amino acid peptide co-secreted from enteroendocrine L cells along with glucagon-like peptide 1 (GLP-1) and has a range of actions via the GLP-2R, which is particularly expressed in the gastrointestinal tract, the liver, adipose tissue, and the central nervous system (CNS). In humans, GLP-2 evidently induces intestinotrophic effects (i.e., induction of intestinal mucosal proliferation and improved gut barrier function) and promotes mesenteric blood flow. However, GLP-2 does not seem to have appetite or food intake-reducing effects in humans, but its gut barrier-promoting effect may be of interest in the context of obesity. Obesity is associated with reduced gut barrier function, increasing the translocation of proinflammatory gut content to the circulation. This phenomenon constitutes a strong driver of obesity-associated systemic low-grade inflammation, which in turn plays a major role in the development of most obesity-associated complications. Thus, the intestinotrophic and gut barrier-improving effect of GLP-2, which in obese rodent models shows strong anti-inflammatory potential, may, in combination with food intake-reducing strategies, e.g., GLP-1 receptor (GLP-1) agonism, be able to rectify core pathophysiological mechanism of obesity. Here, we provide an overview of GLP-2 physiology in the context of obesity pathophysiology and review the pharmacological potential of GLP-2R activation in the management of obesity and related comorbidities.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"177 ","pages":"Article 171210"},"PeriodicalIF":3.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000639/pdfft?md5=a7999597c0a995b795d7cb5be4d5abde&pid=1-s2.0-S0196978124000639-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140350862","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

Intranasal oxytocin as a treatment for anxiety and autism: From subclinical to clinical applications 鼻内催产素作为焦虑症和自闭症的治疗方法：从亚临床应用到临床应用

IF 3 4区医学

Peptides Pub Date : 2024-04-03 DOI: 10.1016/j.peptides.2024.171211

Hailian Yin , Meiyun Jiang , Tao Han , Xiaolei Xu

{"title":"Intranasal oxytocin as a treatment for anxiety and autism: From subclinical to clinical applications","authors":"Hailian Yin , Meiyun Jiang , Tao Han , Xiaolei Xu","doi":"10.1016/j.peptides.2024.171211","DOIUrl":"https://doi.org/10.1016/j.peptides.2024.171211","url":null,"abstract":"<div><p>Animal and human studies have demonstrated that intranasal oxytocin (OT) can penetrate the brain and induce cognitive, emotional, and behavioral changes, particularly in social functioning. Consequently, numerous investigations have explored the potential of OT as a treatment for anxiety and autism, conditions characterized by social deficits. Although both subclinical and clinical studies provide converging evidence of the therapeutic effects of OT in reducing anxiety levels and improving social symptoms in autism, results are not always consistent. Additionally, the pharmacological mechanism of OT requires further elucidation for its effective clinical application. Therefore, this review aims to examine the contentious findings concerning the effects of OT on anxiety and autism, offer interpretations of the inconsistent results from the perspectives of individual differences and varying approaches to OT administration, and shed light on the underlying mechanisms of OT. Ultimately, standardization of dosage, frequency of administration, formulation characteristics, and nasal spray devices is proposed as essential for future human studies and clinical applications of OT treatment.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"176 ","pages":"Article 171211"},"PeriodicalIF":3.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140347922","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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