Journal of molecular endocrinology最新文献

Anti-inflammatory effects of palm11-PrRP31 in a rat model of lipopolysaccharide-induced acute inflammation. 棕榈11-PrRP31在脂多糖诱发急性炎症大鼠模型中的抗炎作用

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2025-01-01 DOI: 10.1530/JME-24-0090

Lucia Mráziková, Silvie Hojna, Anna Shánělová, Blanka Zelezna, Jaroslav Kunes, Lenka Maletinska

{"title":"Anti-inflammatory effects of palm11-PrRP31 in a rat model of lipopolysaccharide-induced acute inflammation.","authors":"Lucia Mráziková, Silvie Hojna, Anna Shánělová, Blanka Zelezna, Jaroslav Kunes, Lenka Maletinska","doi":"10.1530/JME-24-0090","DOIUrl":"https://doi.org/10.1530/JME-24-0090","url":null,"abstract":"Lipopolysaccharides (LPS) are major components of Gram-negative bacteria. LPS not only induce endotoxemia and inflammation, but also contribute to various diseases. In experimental settings, LPS administration serves as a model for acute inflammatory responses. This study aims to evaluate the anti-inflammatory potential and mechanism of action of palmitoylated prolactin-releasing peptide (palm11-PrRP31) in a rat model of LPS-induced inflammation. Palm11-PrRP31 has demonstrated its efficacy in mitigating LPS-induced weight loss and anorexia, emphasizing its potential protective effects. Cytokine profiles revealed a consistent reduction in tumor necrosis factor α, highlighting the potent anti-inflammatory effects of palm11-PrRP31. The peptide also modulated key cytokines and chemokines in plasma, the liver, and the hypothalamus, reflecting its broad-spectrum anti-inflammatory properties. Palm11-PrRP31 also effectively attenuated the expression levels of TLR4 signaling components in the liver, suggesting its suppressive effects on the activation of these pathways during LPS-induced inflammation. These anti-inflammatory effects were specific to palm11-PrRP31, whereas natural PrRP31 had minimal impact. In conclusion, this study reveals the efficacy of palm11-PrRP31 in modulating LPS-induced inflammation, offering insights into its immunomodulatory properties. The abilities of the peptide to suppress proinflammatory responses and attenuate relevant signaling pathways indicate its potential use as a therapeutic agent for inflammatory disorders.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052745","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

Dicer inhibition delays wound closure by increasing SUZ12 levels and regulating ITGAV levels in keratinocytes. Dicer抑制通过增加角化细胞中SUZ12水平和调节ITGAV水平来延迟伤口愈合。

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2025-01-01 DOI: 10.1530/JME-24-0122

Sushant Bhattacharya, Shruti Hazra, Malabika Datta

{"title":"Dicer inhibition delays wound closure by increasing SUZ12 levels and regulating ITGAV levels in keratinocytes.","authors":"Sushant Bhattacharya, Shruti Hazra, Malabika Datta","doi":"10.1530/JME-24-0122","DOIUrl":"https://doi.org/10.1530/JME-24-0122","url":null,"abstract":"Delayed wound closure is a significant hallmark associated with diabetes. A previous study from our laboratory identified decreased levels of Dicer and miRNAs together with altered levels of wound healing genes in the wounded tissues of diabetic rats. Comprehensive regulators of these wound healing genes mapped onto the PRC2 (polycomb repressive complex 2) complex. Here we show that Dicer inhibition increases the transcript levels of core components of the PRC2 complex, namely Suz12 (suppressor of zeste 12) and Ezh2 (enhancer of zeste 2) and of Mtf2 (metal response element-binding transcription factor 2), its additional subunit, and elevates H3K27me3 levels in HaCaT cells. Such patterns of increase were also observed in the wounded tissues of diabetic rats as compared to those of normal rats. In a scratch assay in HaCaT cells, while Dicer inhibition significantly prevented wound closure, this was rescued by Suz12 siRNA but not by Ezh2 inhibition, suggesting that Suz12 mediates the effects of Dicer siRNA in these cells. In addition, as compared to scramble transfected cells, Dicer siRNA decreased the levels of integrin alphaV (Itgav), that is extensively implicated in the process of wound healing and this effect was rescued in the presence of Suz12 siRNA. Itgav harbors potential histone methylation marks across the gene length and Dicer inhibition, by increasing PRC2-mediated H3K27 methylation on Itgav, possibly decreases its transcription that subsequently impairs wound closure. These data put forth novel aspects of delayed wound closure as seen during diabetes and might be a potential target for therapeutic intervention.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978975","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 role of mu-opioid receptors in pancreatic islet α-cells. 胰岛α细胞中缪阿片受体的作用

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2024-12-20 Print Date: 2025-01-01 DOI: 10.1530/JME-24-0060

Chen Kong, Daniel C Castro, Jeongmin Lee, David W Piston

{"title":"The role of mu-opioid receptors in pancreatic islet α-cells.","authors":"Chen Kong, Daniel C Castro, Jeongmin Lee, David W Piston","doi":"10.1530/JME-24-0060","DOIUrl":"10.1530/JME-24-0060","url":null,"abstract":"Diabetes is a complex disease that impacts more than 500 million people across the world. Many of these individuals will develop diabetic neuropathy as a comorbidity, which is historically treated with exogenous opioids, such as morphine, oxycodone, or tramadol. Although these opioids are effective analgesics, growing evidence indicates that they may directly impact the endocrine pancreas function in patients. One common feature of these exogenous opioid ligands is their preference for the mu-opioid receptor (MOPR), so we aimed to determine whether endogenous MOPRs directly regulate pancreatic islet metabolism and hormone secretion. We show that pharmacological antagonism of MOPRs enhances glucagon secretion, but not insulin secretion, from human islets under high-glucose conditions. This increased secretion is accompanied by increased cAMP signaling. mRNA expression of MOPRs is robust in nondiabetic human islets but downregulated in islets from T2D donors, suggesting a link between metabolism and MOPR expression. Conditional genetic knockout of MOPRs in murine α-cells increases glucagon secretion under high-glucose conditions without increasing glucagon content. Consistent with downregulation of MOPRs during metabolic disease, conditional MOPR knockout mice treated with a high-fat diet show impaired glucose tolerance, increased glucagon secretion, increased insulin content, and increased islet size. Together, these results demonstrate a direct mechanism of action for endogenous opioid regulation of endocrine pancreas.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546030","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

Syndecans modulate ghrelin receptor signaling. Syndecans能调节胃泌素受体的信号转导。

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2024-12-19 Print Date: 2025-01-01 DOI: 10.1530/JME-24-0070

Karina Prins, Noa Mutsters, Femke Volker, Martin Huisman, Rosinda Mies, Patric J D Delhanty, Jenny A Visser

{"title":"Syndecans modulate ghrelin receptor signaling.","authors":"Karina Prins, Noa Mutsters, Femke Volker, Martin Huisman, Rosinda Mies, Patric J D Delhanty, Jenny A Visser","doi":"10.1530/JME-24-0070","DOIUrl":"10.1530/JME-24-0070","url":null,"abstract":"Ghrelin is a gut hormone that enhances food intake and growth hormone secretion through its G-protein coupled receptor, the growth hormone secretagogue receptor (GHSR). Recently, we have shown that ghrelin interacts with syndecans (SDCs), a family of membrane proteins known to modulate hypothalamic appetite signaling. Here, we investigated whether SDCs impact ghrelin signaling at GHSR by assessing ghrelin-induced intracellular Ca2+ mobilization (iCa2+) and inositol phosphate 1 (IP1) production in HEK293 cells. Compared with controls, the overexpression of SDCs dose-dependently increased the maximum iCa2+ response two- to four-fold, without affecting EC50. The IP1 response was similarly amplified by SDCs, but it also indicated that they reduce constitutive (ghrelin-independent) activity of GHSR. These enhanced responses occurred despite a SDC dose-dependent reduction in plasma membrane GHSR levels. Although ghrelin-stimulated Gαq activation was unaltered by SDC1 expression, it failed to restore iCa2+ responsiveness in GNAQ/11 knockout cells, indicating dependence on Gαq/11, not another Gα subunit. This suggests that SDCs modulate either signaling downstream of Gαq/11 or quenching of β-arrestin2 recruitment to GHSR. Indeed, expression of SDCs at levels that only modestly suppress cell surface receptor reduced ghrelin-induced β-arrestin2 recruitment by ∼80%. SDC co-expression also delayed the peak β-arrestin2 response. However, peak β-arrestin2 recruitment follows the peak iCa2+ response, making it unclear whether reduced β-arrestin2 recruitment potentiated Ca2+ signaling. Altogether, SDCs enhanced iCa2+/IP1 and reduced β-arrestin2 recruitment by GHSR in response to ghrelin, likely by modulating signaling downstream of Gαq. This could be a novel mechanism through which SDCs affect metabolism and obesity.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676058","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

Continuing the success of Journal of Endocrinology and Journal of Molecular Endocrinology: Editor-in-Chief handover. 延续《内分泌学杂志》和《分子内分泌学杂志》的成功：主编交接。

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2024-12-18 Print Date: 2025-01-01 DOI: 10.1530/JME-24-0124

Martin Haluzik, Gabriela da Silva Xavier

引用次数: 0

Establishment of Star-edited Y1 cells as a novel in vitro functional assay for STAR. 建立星编辑 Y1 细胞，作为 STAR 的新型体外功能测试。

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2024-10-29 Print Date: 2024-11-01 DOI: 10.1530/JME-24-0009

Takeshi Sato, Satoshi Narumi, Tetsushi Sakuma, Kazuhiro Shimura, Yosuke Ichihashi, Takashi Yamamoto, Tomohiro Ishii, Tomonobu Hasegawa

{"title":"Establishment of Star-edited Y1 cells as a novel in vitro functional assay for STAR.","authors":"Takeshi Sato, Satoshi Narumi, Tetsushi Sakuma, Kazuhiro Shimura, Yosuke Ichihashi, Takashi Yamamoto, Tomohiro Ishii, Tomonobu Hasegawa","doi":"10.1530/JME-24-0009","DOIUrl":"10.1530/JME-24-0009","url":null,"abstract":"Genetic variants involving steroidogenic acute regulatory protein cause lipoid congenital adrenal hyperplasia, which is characterized by impaired steroidogenesis in the adrenal glands and gonads. Functional assessment of variant STAR proteins is necessary for an accurate genetic diagnosis. Ideally, steroidogenic cells should be used to assess the functionality of STAR proteins, but the presence of endogenous STARs in steroidogenic cells precludes such a method. Here, we generated Star-edited cells from steroidogenic Y1 mouse adrenocortical tumor cells by genome editing. Star-edited Y1 cells exhibited very low but measurable cAMP-dependent pregnenolone production. Furthermore, stimulation of the cAMP pathway for 2 weeks resulted in the formation of lipid droplets in the cytoplasm of Star-edited Y1 cells, which resembled the histology of the adrenal glands of patients with lipoid congenital adrenal hyperplasia. The steroidogenic defect of Star-edited Y1 cells can be restored by transient overexpression of mouse Star. We found that human STAR can also restore defective steroidogenesis in Star-edited Y1 cells, and we were able to construct a novel in vitro system to evaluate human STAR variants. Collectively, we established Star-edited Y1 cells that retain the steroidogenic pathway downstream of the Star protein. Star-edited Y1 cells recapitulate the functional and morphological changes of lipoid congenital adrenal hyperplasia and can be used to evaluate the functionality of human STAR variants.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348518","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

CREB activates the MafA promoter through proximal E-boxes and a CCAAT motif in pancreatic β-cells. 在胰腺β细胞中，CREB 通过近端 E-boxes 和 CCAAT motif 激活 MafA 启动子。

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2024-10-04 Print Date: 2024-10-01 DOI: 10.1530/JME-24-0023

Yuki Aida, Kohsuke Kataoka

{"title":"CREB activates the MafA promoter through proximal E-boxes and a CCAAT motif in pancreatic β-cells.","authors":"Yuki Aida, Kohsuke Kataoka","doi":"10.1530/JME-24-0023","DOIUrl":"10.1530/JME-24-0023","url":null,"abstract":"MafA is a key transcriptional regulator of pancreatic islet β-cell function. Its target genes include those encoding preproinsulin and the glucose transporter Glut2 (Slc2a2); thus, MafA function is essential for glucose-stimulated insulin secretion. Expression levels of MafA are reduced in β-cells of diabetic mouse models and human subjects, suggesting that β-cell dysfunction associated with type 2 diabetes is attributable to the loss of MafA. On the other hand, MafA is transcriptionally upregulated by incretin hormones through activation of CREB and its co-activator CRTC2. β-cell-specific expression of MafA relies on a distal enhancer element. However, the precise mechanism by which CREB-CRTC2 regulates the enhancer and proximal promoter regions of MafA remains unclear. In this report, we analyzed previously published ChIP-seq data and found that CREB and NeuroD1, a β-cell-enriched transactivator, bound to both the promoter and enhancer regions of human MAFA. A series of reporter assays revealed that CREB activated the enhancer through a conserved cAMP-responsive element (CRE) but stimulated MAFA promoter activity even when the putative CRE was deleted. Two E-box elements and a CCAAT motif, which bind NeuroD1 and ubiquitous NF-Y transcription factors, respectively, were necessary for transcriptional activation of the MAFA promoter by CREB. Genome-wide analysis of CREB-bound loci in β-cells revealed that they were enriched with CCAAT motifs. Furthermore, promoter analysis of the Isl1 gene encoding a β-cell-enriched transcription factor revealed that a CRE-like element and two CCAAT motifs, but not the E-box, were necessary for activation by CREB. These results provide clues to elucidate the detailed mechanism by which CREB regulates MafA as well as β-cell-specific genes.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073105","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

Multiple promoter and enhancer differences likely contribute to augmented G6PC2 expression in human versus mouse pancreatic islet alpha cells. 多种启动子和增强子差异很可能导致 G6PC2 在人与小鼠胰岛α细胞中的表达增强。

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2024-09-18 Print Date: 2024-10-01 DOI: 10.1530/JME-24-0051

Cyrus C Martin, James K Oeser, Tenzin Wangmo, Brian P Flemming, Alan D Attie, Mark P Keller, Richard M O'Brien

{"title":"Multiple promoter and enhancer differences likely contribute to augmented G6PC2 expression in human versus mouse pancreatic islet alpha cells.","authors":"Cyrus C Martin, James K Oeser, Tenzin Wangmo, Brian P Flemming, Alan D Attie, Mark P Keller, Richard M O'Brien","doi":"10.1530/JME-24-0051","DOIUrl":"10.1530/JME-24-0051","url":null,"abstract":"G6PC2 encodes a glucose-6-phosphatase catalytic subunit that opposes the action of glucokinase in pancreatic islets, thereby modulating the sensitivity of insulin and glucagon secretion to glucose. In mice, G6pc2 is expressed at ~20-fold higher levels in β-cells than in α-cells, whereas in humans G6PC2 is expressed at only ~5-fold higher levels in β-cells. We therefore hypothesize that G6PC2 likely influences glucagon secretion to a greater degree in humans. With a view to generating a humanized mouse that recapitulates augmented G6PC2 expression levels in α-cells, we sought to identify the genomic regions that confer differential mouse G6pc2 expression in α-cells versus β-cells as well as the evolutionary changes that have altered this ratio in humans. Studies in islet-derived cell lines suggest that the elevated G6pc2 expression in mouse β-cells versus α-cells is mainly due to a difference in the relative activity of the proximal G6pc2 promoter in these cell types. Similarly, the smaller difference in G6PC2 expression between α-cells and β-cells in humans is potentially explained by a change in relative proximal G6PC2 promoter activity. However, we show that both glucocorticoid levels and multiple differences in the relative activity of eight transcriptional enhancers between mice and humans likely contribute to differential G6PC2 expression. Finally, we show that a mouse-specific non-coding RNA, Gm13613, whose expression is controlled by G6pc2 enhancer I, does not regulate G6pc2 expression, indicating that altered expression of Gm13613 in a humanized mouse that contains both the human promoter and enhancers should not affect G6PC2 function.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909929","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

Icariside II protects from marrow adipose tissue (MAT) expansion in estrogen-deficient mice by targeting S100A16. 淫羊藿苷 II 通过靶向 S100A16 保护雌激素缺乏小鼠的骨髓脂肪组织 (MAT) 免受扩张。

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2024-09-18 Print Date: 2024-10-01 DOI: 10.1530/JME-24-0020

Dong Li, Chenhao Cao, Zhuofan Li, Zhiyong Chang, Ping Cai, Chenxi Zhou, Jun Liu, Kaihua Li, Bin Du

{"title":"Icariside II protects from marrow adipose tissue (MAT) expansion in estrogen-deficient mice by targeting S100A16.","authors":"Dong Li, Chenhao Cao, Zhuofan Li, Zhiyong Chang, Ping Cai, Chenxi Zhou, Jun Liu, Kaihua Li, Bin Du","doi":"10.1530/JME-24-0020","DOIUrl":"10.1530/JME-24-0020","url":null,"abstract":"Icariside II, a flavonoid glycoside, is the main component found invivo after the administration of Herba epimedii and has shown some pharmacological effects, such as prevention of osteoporosis and enhancement of immunity. Increased levels of marrow adipose tissue are associated with osteoporosis. S100 calcium-binding protein A16 (S100A16) promotes the differentiation of bone marrow mesenchymal stem cells (BMSCs) into adipocytes. This study aimed to confirm the anti-lipidogenesis effect of Icariside II in the bone marrow by inhibiting S100A16 expression. We used ovariectomy (OVX) and BMSC models. The results showed that Icariside II reduced bone marrow fat content and inhibited BMSCs adipogenic differentiation and S100A16 expression, which correlated with lipogenesis. Overexpression of S100A16 eliminated the inhibitory effect of Icariside II on lipid formation. β-catenin participated in the regulation adipogenesis mediated by Icariside II/S100A16 in the bone. In conclusion, Icariside II protects against OVX-induced bone marrow adipogenesis by downregulating S100A16, in which β-catenin might also be involved.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889503","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

The role of receptor activity-modifying proteins in obesity and diabetes mellitus 受体活性修饰蛋白在肥胖症和糖尿病中的作用

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2024-09-01 DOI: 10.1530/jme-24-0056

Milena A Malcharek, Abigail Pearce, Cheryl A Brighton, David C Hornigold, Graham Ladds

{"title":"The role of receptor activity-modifying proteins in obesity and diabetes mellitus","authors":"Milena A Malcharek, Abigail Pearce, Cheryl A Brighton, David C Hornigold, Graham Ladds","doi":"10.1530/jme-24-0056","DOIUrl":"https://doi.org/10.1530/jme-24-0056","url":null,"abstract":"Receptor activity-modifying proteins (RAMPs) modulate the expression and activity of numerous G protein-coupled receptors, primarily those within class B1. These receptors have important physiological roles, including in the regulation of food intake, energy metabolism, and glucose homeostasis. Dysregulation of these pathways can lead to obesity and diabetes mellitus, which present an ever-expanding global challenge. Whilst the roles of class B1 receptors and their peptide agonists in obesity and diabetes have been investigated, the contribution of RAMPs is less well understood. This review summarises the results of RAMP knockout studies, highlighting the involvement of these proteins in the incidence of disease. It then moves to discuss how receptor, RAMP, and agonist expression changes in disease states, and the benefits (or detriments) of these agonists to the pathways implicated in disease pathophysiology. Whilst much of the data centres around the calcitonin family of receptors, as their interactions with RAMPs are well established, this review then discusses receptors whose role in obesity and diabetes is well founded, but the significance of whose interactions with RAMPs is more recently emerging. The conclusion of this study of the literature is, however, that the information surrounding RAMPs is conflicting and multifaceted, and more research is required to fully understand their contribution to obesity and diabetes.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"39 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264988","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