Pub Date : 2024-04-03DOI: 10.1016/j.peptides.2024.171211
Hailian Yin , Meiyun Jiang , Tao Han , Xiaolei Xu
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.
动物和人体研究表明,鼻内催产素(OT)可渗透大脑,诱发认知、情感和行为变化,尤其是在社交功能方面。因此,许多研究都在探索催产素治疗焦虑症和自闭症的潜力。虽然亚临床研究和临床研究都提供了一致的证据,证明加压疗法在降低焦虑水平和改善自闭症社交症状方面具有治疗效果,但结果并不总是一致的。此外,OT 的药理机制需要进一步阐明,才能有效地应用于临床。因此,本综述旨在研究有关催产素对焦虑和自闭症影响的争议性研究结果,从个体差异和不同催产素用药方法的角度对不一致的结果进行解释,并阐明催产素的内在机制。最后,我们提出剂量、给药频率、配方特点和鼻腔喷雾装置的标准化对于未来的人体研究和 OT 治疗的临床应用至关重要。
{"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":null,"pages":null},"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}
By activating the stress system, stress modulates various physiological parameters including food intake, energy consumption, and, consequently, body weight. The role of oxytocin in the regulation of stress and obesity cannot be disregarded. Based on these findings, we aimed to investigate the effect of intranasal oxytocin on stress response in high-fat-diet (HFD)--fed and control-diet-fed rats exposed to chronic stress. Cold-immobilization stress was applied for 5 consecutive days to male Sprague-Dawley rats fed either with a control diet (n=20) or HFD (n=20) for 6 weeks. Half of the animals in each group received oxytocin. Stress response was evaluated via plasma and salivary cortisol levels as well as elevated plus maze scores. Prefrontal cortex and hypothalamic oxytocin receptor (OxtR) expression levels were identified using western blot analysis. The results showed higher stress response in HFD-fed animals than in control animals both under basal and post-stress conditions. Oxytocin application had a prominent anxiolytic effect in the control group but an insignificant effect in the HFD group. While OxtR expression levels in the prefrontal cortex did not vary according to the body weight and oxytocin application, OxtR levels in the hypothalamus were higher in the HFD- and/or oxytocin-treated animals. Our results indicated that the peripheral and central effects of oxytocin vary with body weight. Moreover, obesity masks the anxiolytic effects of oxytocin, probably by reinforcing the stress condition via central OxtRs. In conclusion, elucidating the mechanisms underlying the central effect of oxytocin is important to cope with stress and obesity.
通过激活应激系统,应激可调节各种生理参数,包括食物摄入量、能量消耗以及体重。催产素在压力和肥胖调节中的作用不容忽视。基于这些发现,我们旨在研究鼻内催产素对暴露于慢性应激的高脂饮食(HFD)喂养大鼠和对照饮食喂养大鼠的应激反应的影响。连续5天对雄性Sprague-Dawley大鼠施加冷固定应激,喂食对照组(20只)或高脂饮食组(20只),喂食时间为6周。每组有一半动物接受催产素治疗。应激反应通过血浆和唾液皮质醇水平以及高架迷宫得分进行评估。通过 Western 印迹分析确定了前额叶皮层和下丘脑催产素受体(OxtR)的表达水平。结果表明,在基础和应激后条件下,喂食高纤维食物的动物的应激反应均高于对照组动物。施用催产素对对照组有明显的抗焦虑作用,但对高密度脂蛋白组的作用不明显。虽然前额叶皮层中的OxtR表达水平并不随体重和催产素的应用而变化,但下丘脑中的OxtR水平在HFD和/或催产素处理的动物中较高。我们的研究结果表明,催产素的外周和中枢效应随体重而变化。此外,肥胖掩盖了催产素的抗焦虑作用,可能是通过中枢OxtRs加强了应激状态。总之,阐明催产素中枢效应的机制对于应对压力和肥胖非常重要。
{"title":"Body weight modulates the impact of oxytocin on chronic cold-immobilization stress response","authors":"Deniz Önal , Hilal Korkmaz , Gizem Önal , Bilge Pehlivanoğlu","doi":"10.1016/j.peptides.2024.171202","DOIUrl":"10.1016/j.peptides.2024.171202","url":null,"abstract":"<div><p>By activating the stress system, stress modulates various physiological parameters including food intake, energy consumption, and, consequently, body weight. The role of oxytocin in the regulation of stress and obesity cannot be disregarded. Based on these findings, we aimed to investigate the effect of intranasal oxytocin on stress response in high-fat-diet (HFD)--fed and control-diet-fed rats exposed to chronic stress. Cold-immobilization stress was applied for 5 consecutive days to male Sprague-Dawley rats fed either with a control diet (n=20) or HFD (n=20) for 6 weeks. Half of the animals in each group received oxytocin. Stress response was evaluated via plasma and salivary cortisol levels as well as elevated plus maze scores. Prefrontal cortex and hypothalamic oxytocin receptor (OxtR) expression levels were identified using western blot analysis. The results showed higher stress response in HFD-fed animals than in control animals both under basal and post-stress conditions. Oxytocin application had a prominent anxiolytic effect in the control group but an insignificant effect in the HFD group. While OxtR expression levels in the prefrontal cortex did not vary according to the body weight and oxytocin application, OxtR levels in the hypothalamus were higher in the HFD- and/or oxytocin-treated animals. Our results indicated that the peripheral and central effects of oxytocin vary with body weight. Moreover, obesity masks the anxiolytic effects of oxytocin, probably by reinforcing the stress condition via central OxtRs. In conclusion, elucidating the mechanisms underlying the central effect of oxytocin is important to cope with stress and obesity.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331954","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}
Pub Date : 2024-03-29DOI: 10.1016/j.peptides.2024.171201
Christopher L. Schaich , Daniel E. Leisman , Marcia B. Goldberg , Micheal R. Filbin , Ashish K. Khanna , Mark C. Chappell
Sepsis and septic shock are global healthcare problems associated with mortality rates of up to 40% despite optimal standard-of-care therapy and constitute the primary cause of death in intensive care units worldwide. Circulating biomarkers of septic shock severity may represent a clinically relevant approach to individualize those patients at risk for worse outcomes early in the course of the disease, which may facilitate early and more precise interventions to improve the clinical course. However, currently used septic shock biomarkers, including lactate, may be non-specific and have variable impact on prognosis and/or disease management. Activation of the renin-angiotensin-aldosterone system (RAAS) is likely an early event in septic shock, and studies suggest that an elevated level of renin, the early and committed step in the RAAS cascade, is a better predictor of worse outcomes in septic shock, including mortality, than the current standard-of-care measure of lactate. Despite a robust increase in renin, other elements of the RAAS, including endogenous levels of Ang II, may fail to sufficiently increase to maintain blood pressure, tissue perfusion, and protective immune responses in septic shock patients. We review the current clinical literature regarding the dysfunction of the RAAS in septic shock and potential therapeutic approaches to improve clinical outcomes.
脓毒症和脓毒性休克是全球性的医疗保健问题,尽管采用了最佳的标准护理疗法,但死亡率仍高达 40%,是全球重症监护病房的主要死亡原因。脓毒性休克严重程度的循环生物标志物可能是一种与临床相关的方法,可用于在疾病早期对有恶化风险的患者进行个体化治疗,这将有助于及早采取更精确的干预措施来改善临床病程。然而,目前使用的脓毒性休克生物标志物(包括乳酸)可能是非特异性的,对预后和/或疾病管理的影响也不尽相同。肾素-血管紧张素-醛固酮系统(RAAS)的激活很可能是脓毒性休克的早期事件,研究表明,肾素是 RAAS 级联的早期和关键步骤,与目前的标准指标乳酸盐相比,肾素水平的升高能更好地预测脓毒性休克的不良预后,包括死亡率。尽管肾素强劲增长,但 RAAS 的其他要素(包括内源性 Ang II 水平)可能无法充分增长以维持脓毒性休克患者的血压、组织灌注和保护性免疫反应。我们回顾了目前有关脓毒性休克 RAAS 功能障碍的临床文献,以及改善临床预后的潜在治疗方法。
{"title":"Dysfunction of the renin-angiotensin-aldosterone system in human septic shock","authors":"Christopher L. Schaich , Daniel E. Leisman , Marcia B. Goldberg , Micheal R. Filbin , Ashish K. Khanna , Mark C. Chappell","doi":"10.1016/j.peptides.2024.171201","DOIUrl":"10.1016/j.peptides.2024.171201","url":null,"abstract":"<div><p>Sepsis and septic shock are global healthcare problems associated with mortality rates of up to 40% despite optimal standard-of-care therapy and constitute the primary cause of death in intensive care units worldwide. Circulating biomarkers of septic shock severity may represent a clinically relevant approach to individualize those patients at risk for worse outcomes early in the course of the disease, which may facilitate early and more precise interventions to improve the clinical course. However, currently used septic shock biomarkers, including lactate, may be non-specific and have variable impact on prognosis and/or disease management. Activation of the renin-angiotensin-aldosterone system (RAAS) is likely an early event in septic shock, and studies suggest that an elevated level of renin, the early and committed step in the RAAS cascade, is a better predictor of worse outcomes in septic shock, including mortality, than the current standard-of-care measure of lactate. Despite a robust increase in renin, other elements of the RAAS, including endogenous levels of Ang II, may fail to sufficiently increase to maintain blood pressure, tissue perfusion, and protective immune responses in septic shock patients. We review the current clinical literature regarding the dysfunction of the RAAS in septic shock and potential therapeutic approaches to improve clinical outcomes.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331955","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}
Pub Date : 2024-03-28DOI: 10.1016/j.peptides.2024.171200
Nadya M. Morrow , Arianne Morissette , Erin E. Mulvihill
Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are peptide hormones produced by enteroendocrine cells in the small intestine. Despite being produced in the gut, the leveraging of their role in potentiating glucose-stimulated insulin secretion, also known as the incretin effect, has distracted from discernment of direct intestinal signaling circuits. Both preclinical and clinical evidence have highlighted a role for the incretins in inflammation. In this review, we highlight the discoveries of GLP-1 receptor (GLP-1R)+ natural (TCRαβ and TCRγδ) and induced (TCRαβ+CD4+ cells and TCRαβ+CD8αβ+) intraepithelial lymphocytes. Both endogenous signaling and pharmacological activation of GLP-1R impact local and systemic inflammation, the gut microbiota, whole-body metabolism, as well as the control of GLP-1 bioavailability. While GIPR signaling has been documented to impact hematopoiesis, the impact of these bone marrow-derived cells in gut immunology is not well understood. We uncover gaps in the literature of the evaluation of the impact of sex in these GLP-1R and GIP receptor (GIPR) signaling circuits and provide speculations of the maintenance roles these hormones play within the gut in the fasting-refeeding cycles. GLP-1R agonists and GLP-1R/GIPR agonists are widely used as treatments for diabetes and weight loss, respectively; however, their impact on gut homeostasis has not been fully explored. Advancing our understanding of the roles of GLP-1R and GIPR signaling within the gut at homeostasis as well as metabolic and inflammatory diseases may provide targets to improve disease management.
{"title":"Immunomodulation and inflammation: Role of GLP-1R and GIPR expressing cells within the gut","authors":"Nadya M. Morrow , Arianne Morissette , Erin E. Mulvihill","doi":"10.1016/j.peptides.2024.171200","DOIUrl":"10.1016/j.peptides.2024.171200","url":null,"abstract":"<div><p>Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are peptide hormones produced by enteroendocrine cells in the small intestine. Despite being produced in the gut, the leveraging of their role in potentiating glucose-stimulated insulin secretion, also known as the incretin effect, has distracted from discernment of direct intestinal signaling circuits. Both preclinical and clinical evidence have highlighted a role for the incretins in inflammation. In this review, we highlight the discoveries of GLP-1 receptor (GLP-1R)+ natural (TCRαβ and TCRγδ) and induced (TCRαβ+CD4+ cells and TCRαβ+CD8αβ+) intraepithelial lymphocytes. Both endogenous signaling and pharmacological activation of GLP-1R impact local and systemic inflammation, the gut microbiota, whole-body metabolism, as well as the control of GLP-1 bioavailability. While GIPR signaling has been documented to impact hematopoiesis, the impact of these bone marrow-derived cells in gut immunology is not well understood. We uncover gaps in the literature of the evaluation of the impact of sex in these GLP-1R and GIP receptor (GIPR) signaling circuits and provide speculations of the maintenance roles these hormones play within the gut in the fasting-refeeding cycles. GLP-1R agonists and GLP-1R/GIPR agonists are widely used as treatments for diabetes and weight loss, respectively; however, their impact on gut homeostasis has not been fully explored. Advancing our understanding of the roles of GLP-1R and GIPR signaling within the gut at homeostasis as well as metabolic and inflammatory diseases may provide targets to improve disease management.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330050","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}
It has been known since 2005 that the secretion of several gut hormones changes radically after gastric bypass operations and, although more moderately, after sleeve gastrectomy but not after gastric banding. It has therefore been speculated that increased secretion of particularly GLP-1 and Peptide YY (PYY), which both inhibit appetite and food intake, may be involved in the weight loss effects of surgery and for improvements in glucose tolerance. Experiments involving inhibition of hormone secretion with somatostatin, blockade of their actions with antagonists, or blockade of hormone formation/activation support this notion. However, differences between results of bypass and sleeve operations indicate that distinct mechanisms may also be involved. Although the reductions in ghrelin secretion after sleeve gastrectomy would seem to provide an obvious explanation, experiments with restoration of ghrelin levels pointed towards effects on insulin secretion and glucose tolerance rather than on food intake. It seems clear that changes in GLP-1 secretion are important for insulin secretion after bypass and appear to be responsible for postbariatric hypoglycemia in glucose-tolerant individuals; however, with time the improvements in insulin sensitivity, which in turn are secondary to the weight loss, may be more important. Changes in bile acid metabolism do not seem to be of particular importance in humans.
{"title":"New Lessons from the gut: Studies of the role of gut peptides in weight loss and diabetes resolution after gastric bypass and sleeve gastrectomy","authors":"Jens Juul Holst , Sten Madsbad , Kirstine Nyvold Bojsen-Møller , Carsten Dirksen , Maria Svane","doi":"10.1016/j.peptides.2024.171199","DOIUrl":"10.1016/j.peptides.2024.171199","url":null,"abstract":"<div><p>It has been known since 2005 that the secretion of several gut hormones changes radically after gastric bypass operations and, although more moderately, after sleeve gastrectomy but not after gastric banding. It has therefore been speculated that increased secretion of particularly GLP-1 and Peptide YY (PYY), which both inhibit appetite and food intake, may be involved in the weight loss effects of surgery and for improvements in glucose tolerance. Experiments involving inhibition of hormone secretion with somatostatin, blockade of their actions with antagonists, or blockade of hormone formation/activation support this notion. However, differences between results of bypass and sleeve operations indicate that distinct mechanisms may also be involved. Although the reductions in ghrelin secretion after sleeve gastrectomy would seem to provide an obvious explanation, experiments with restoration of ghrelin levels pointed towards effects on insulin secretion and glucose tolerance rather than on food intake. It seems clear that changes in GLP-1 secretion are important for insulin secretion after bypass and appear to be responsible for postbariatric hypoglycemia in glucose-tolerant individuals; however, with time the improvements in insulin sensitivity, which in turn are secondary to the weight loss, may be more important. Changes in bile acid metabolism do not seem to be of particular importance in humans.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000524/pdfft?md5=72ecfed8ae45027b259cb41803b79a0e&pid=1-s2.0-S0196978124000524-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140326960","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}
Pub Date : 2024-03-26DOI: 10.1016/j.peptides.2024.171198
Arkadiusz Liskiewicz , Timo D. Müller
In recent years, significant progress has been made to pharmacologically combat the obesity pandemic, particularly with regard to biochemically tailored drugs that simultaneously target the receptors for glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic polypeptide (GIP). But while the pharmacological benefits of GLP-1 receptor (GLP-1R) agonism are widely acknowledged, the role of the GIP system in regulating systems metabolism remains controversial. When given in adjunct to GLP-1R agonism, both agonism and antagonism of the GIP receptor (GIPR) improves metabolic outcome in preclinical and clinical studies, and despite persistent concerns about its potential obesogenic nature, there is accumulating evidence indicating that GIP has beneficial metabolic effects via central GIPR agonism. Nonetheless, despite growing recognition of the GIP system as a valuable pharmacological target, there remains great uncertainty as to where and how GIP acts in the brain to regulate metabolism, and how GIPR agonism may differ from GIPR antagonism in control of energy metabolism. In this review we highlight current knowledge on the central action of GIP, and discuss open questions related to its multifaceted biology in the brain and the periphery.
{"title":"Regulation of energy metabolism through central GIPR signaling","authors":"Arkadiusz Liskiewicz , Timo D. Müller","doi":"10.1016/j.peptides.2024.171198","DOIUrl":"10.1016/j.peptides.2024.171198","url":null,"abstract":"<div><p>In recent years, significant progress has been made to pharmacologically combat the obesity pandemic, particularly with regard to biochemically tailored drugs that simultaneously target the receptors for glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic polypeptide (GIP). But while the pharmacological benefits of GLP-1 receptor (GLP-1R) agonism are widely acknowledged, the role of the GIP system in regulating systems metabolism remains controversial. When given in adjunct to GLP-1R agonism, both agonism and antagonism of the GIP receptor (GIPR) improves metabolic outcome in preclinical and clinical studies, and despite persistent concerns about its potential obesogenic nature, there is accumulating evidence indicating that GIP has beneficial metabolic effects via central GIPR agonism. Nonetheless, despite growing recognition of the GIP system as a valuable pharmacological target, there remains great uncertainty as to where and how GIP acts in the brain to regulate metabolism, and how GIPR agonism may differ from GIPR antagonism in control of energy metabolism. In this review we highlight current knowledge on the central action of GIP, and discuss open questions related to its multifaceted biology in the brain and the periphery.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288709","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}
The pathogenesis of type 2 diabetes (T2D) is associated with dysregulation of glucoregulatory hormones, including both islet and enteroendocrine peptides. Microribonucleic acids (miRNAs) are short noncoding RNA sequences which post transcriptionally inhibit protein synthesis by binding to complementary messenger RNA (mRNA). Essential for normal cell activities, including proliferation and apoptosis, dysregulation of these noncoding RNA molecules have been linked to several diseases, including diabetes, where alterations in miRNA expression within pancreatic islets have been observed. This may occur as a compensatory mechanism to maintain beta-cell mass/function (e.g., downregulation of miR-7), or conversely, lead to further beta-cell demise and disease progression (e.g., upregulation of miR-187). Thus, targeting miRNAs has potential for novel diagnostic and therapeutic applications in T2D. This is reinforced by the success seen to date with miRNA-based therapeutics for other conditions currently in clinical trials. In this review, differential expression of miRNAs in human islets associated with T2D will be discussed along with further consideration of their effects on the production and secretion of islet and incretin hormones. This analysis further unravels the therapeutic potential of miRNAs and offers insights into novel strategies for T2D management.
{"title":"MicroRNA regulation of islet and enteroendocrine peptides: Physiology and therapeutic implications for type 2 diabetes","authors":"E.R. Carr , P.B. Higgins , N.H. McClenaghan , P.R. Flatt , A.G. McCloskey","doi":"10.1016/j.peptides.2024.171196","DOIUrl":"10.1016/j.peptides.2024.171196","url":null,"abstract":"<div><p>The pathogenesis of type 2 diabetes (T2D) is associated with dysregulation of glucoregulatory hormones, including both islet and enteroendocrine peptides. Microribonucleic acids (miRNAs) are short noncoding RNA sequences which post transcriptionally inhibit protein synthesis by binding to complementary messenger RNA (mRNA). Essential for normal cell activities, including proliferation and apoptosis, dysregulation of these noncoding RNA molecules have been linked to several diseases, including diabetes, where alterations in miRNA expression within pancreatic islets have been observed. This may occur as a compensatory mechanism to maintain beta-cell mass/function (e.g., downregulation of miR-7), or conversely, lead to further beta-cell demise and disease progression (e.g., upregulation of miR-187). Thus, targeting miRNAs has potential for novel diagnostic and therapeutic applications in T2D. This is reinforced by the success seen to date with miRNA-based therapeutics for other conditions currently in clinical trials. In this review, differential expression of miRNAs in human islets associated with T2D will be discussed along with further consideration of their effects on the production and secretion of islet and incretin hormones. This analysis further unravels the therapeutic potential of miRNAs and offers insights into novel strategies for T2D management.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0196978124000494/pdfft?md5=66719a82b03af58c6708975250c73b64&pid=1-s2.0-S0196978124000494-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140493","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}
Pub Date : 2024-03-15DOI: 10.1016/j.peptides.2024.171197
Katherine A. Kern , Adrianne M. DiBrog , Kiran Kaur , Johnathan T. Przybysz , Elizabeth G. Mietlicki-Baase
Amylin, a pancreatic hormone, is well-established to suppress feeding by enhancing satiation. Pramlintide, an amylin analog that is FDA-approved for the treatment of diabetes, has also been shown to produce hypophagia. However, the behavioral mechanisms underlying the ability of pramlintide to suppress feeding are unresolved. We hypothesized that systemic pramlintide administration in rats would reduce energy intake, specifically by reducing meal size. Male rats were given b.i.d. administration of intraperitoneal pramlintide or vehicle for 1 week, and chow intake, meal patterns, and body weight were monitored throughout the test period. Consistent with our hypothesis, pramlintide decreased chow intake mainly via suppression of meal size, with corresponding reductions in meal duration on several days. Fewer effects on meal number or feeding rate were detected. Pramlintide also reduced weight gain over the 1-week study. These results highlight that the behavioral mechanisms by which pramlintide produces hypophagia are similar to those driven by amylin itself, and provide important insight into the ability of this pharmacotherapy to promote negative energy balance over a period of chronic administration.
{"title":"Chronic pramlintide decreases feeding via a reduction in meal size in male rats","authors":"Katherine A. Kern , Adrianne M. DiBrog , Kiran Kaur , Johnathan T. Przybysz , Elizabeth G. Mietlicki-Baase","doi":"10.1016/j.peptides.2024.171197","DOIUrl":"10.1016/j.peptides.2024.171197","url":null,"abstract":"<div><p>Amylin, a pancreatic hormone, is well-established to suppress feeding by enhancing satiation. Pramlintide, an amylin analog that is FDA-approved for the treatment of diabetes, has also been shown to produce hypophagia. However, the behavioral mechanisms underlying the ability of pramlintide to suppress feeding are unresolved. We hypothesized that systemic pramlintide administration in rats would reduce energy intake, specifically by reducing meal size. Male rats were given b.i.d. administration of intraperitoneal pramlintide or vehicle for 1 week, and chow intake, meal patterns, and body weight were monitored throughout the test period. Consistent with our hypothesis, pramlintide decreased chow intake mainly via suppression of meal size, with corresponding reductions in meal duration on several days. Fewer effects on meal number or feeding rate were detected. Pramlintide also reduced weight gain over the 1-week study. These results highlight that the behavioral mechanisms by which pramlintide produces hypophagia are similar to those driven by amylin itself, and provide important insight into the ability of this pharmacotherapy to promote negative energy balance over a period of chronic administration.</p></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143900","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}
Pub Date : 2024-03-13DOI: 10.1016/j.peptides.2024.171186
Christopher A. Bannon , Claire L. Meek , Frank Reimann , Fiona M. Gribble
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-03-09DOI: 10.1016/j.peptides.2024.171185
Penelope Trimpou , Ioannis Bounias , Olof Ehn , Ola Hammarsten , Oskar Ragnarsson
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.
{"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":null,"pages":null},"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}