Journal of molecular endocrinology最新文献_第3页

Lack of maternal exposure to somatostatin leads to diet-induced insulin and leptin resistance in mouse male offspring. 缺乏母体生长抑素暴露导致小鼠雄性后代饮食诱导的胰岛素和瘦素抵抗。

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2025-03-22 Print Date: 2025-05-01 DOI: 10.1530/JME-24-0102

Zhongyue Yang, Catherine P Kirschke, Liping Huang

{"title":"Lack of maternal exposure to somatostatin leads to diet-induced insulin and leptin resistance in mouse male offspring.","authors":"Zhongyue Yang, Catherine P Kirschke, Liping Huang","doi":"10.1530/JME-24-0102","DOIUrl":"10.1530/JME-24-0102","url":null,"abstract":"Somatostatin (Sst) is an inhibitory regulator of many hormones. The prenatal environment impacts an offspring's risk to type 2 diabetes in adulthood. However, the effect of maternal Sst deficiency on glucose and insulin metabolism in offspring and metabolic disease risk in their adult life has been poorly understood. The study was to investigate the impact of a lack of maternal Sst exposure in mouse male and female offspring on diet-induced changes in glucose metabolism and adiposity. Sst knockout offspring, SstKO born to the Sst-heterozygous dams or SstKO-MSD born to the Sst-homozygous dams were fed either a regular diet (CD) or a high-fat diet (HFD) at 3-week-old for 15 weeks. Body weight and blood glucose levels were monitored. Glucose and insulin tolerance tests were performed. Plasma hormone levels and gene expression in the hypothalamus were investigated. The results demonstrated that only male SstKO-MSD offspring developed obesity accompanied by severe insulin and leptin resistance after HFD challenge. Insulin secretion was reduced in both basal and oral glucose-challenged conditions in the CD-fed male SstKO-MSD mice. A reduced ratio of islet area to pancreas area was noted in SstKO-MSD mice in both sexes. Plasma levels of glucagon, Glp1 and Pyy were elevated in both male and female SstKO and SstKO-MSD mice. mRNA expression of leptin receptor, FoxO1, Npy and Agrp was downregulated in male SstKO-MSD mice. These results demonstrate that a lack of fetal somatostatin exposure impairs the islet development in offspring and increases risk of obesity, insulin resistance and leptin resistance later in life.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604981","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

Disruption of thyroid-intrinsic clock aggravates experimental autoimmune thyroiditis. 甲状腺内在时钟紊乱加重实验性自身免疫性甲状腺炎。

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2025-03-08 Print Date: 2025-04-01 DOI: 10.1530/JME-25-0022

Jinrong Fu, Rili Gao, Qiting Ye, Wenwen Feng, He Liu, Yushu Li, Haixia Guan

引用次数: 0

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 : 2025-02-14 Print Date: 2025-04-01 DOI: 10.1530/JME-24-0090

Lucia Mráziková, Silvie Hojná, Anna Shánělová, Blanka Železná, Jaroslav Kuneš, Lenka Maletínská

{"title":"Anti-inflammatory effects of palm11-PrRP31 in a rat model of lipopolysaccharide-induced acute inflammation.","authors":"Lucia Mráziková, Silvie Hojná, Anna Shánělová, Blanka Železná, Jaroslav Kuneš, Lenka Maletínská","doi":"10.1530/JME-24-0090","DOIUrl":"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 aimed 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 efficacy in mitigating LPS-induced weight loss and anorexia, emphasizing its potential protective effects. The 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 the plasma, liver and hypothalamus, reflecting its broad-spectrum anti-inflammatory properties. Palm11-PrRP31 also effectively attenuated the expression levels of Toll-like receptor 4 signaling components in the liver, suggesting its ability to suppress the activation of these pathways during LPS-induced inflammation. These anti-inflammatory effects were specific to palm11-PrRP31, whereas natural PrRP31 had a minimal impact. In conclusion, this study reveals the efficacy of palm11-PrRP31 in modulating LPS-induced inflammation, offering insights into its immunomodulatory properties. The ability of the peptide to suppress proinflammatory responses and attenuate relevant signaling pathways indicates its potential use as a therapeutic agent for inflammatory disorders.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840832/pdf/","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":"OA","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 : 2025-01-28 Print Date: 2025-03-01 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":"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 alpha V (Itgav), which is extensively implicated in the process of wound healing, and this effect was rescued in the presence of Suz12 siRNA. Itgav harbours 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":"2025-01-28","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

A missing paradigm: deciphering endocrine innovations among diverging regulations of alleles, paralogous genes and orthologous genes. 一个缺失的范例：在等位基因、旁系和同源基因的不同调控中破译内分泌创新。

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2025-01-11 Print Date: 2025-02-01 DOI: 10.1530/JME-24-0092

Jean-Jacques Lareyre, Philippe Monget

引用次数: 0

Glucocorticoids reduce Slc2a2 (GLUT2) gene expression through HNF1 in pancreatic β-cells. 糖皮质激素通过HNF1降低胰腺β-细胞中Slc2a2 （GLUT2）基因的表达。

IF 3.8 4区医学

Journal of molecular endocrinology Pub Date : 2025-01-10 Print Date: 2025-02-01 DOI: 10.1530/JME-24-0077

Yuka Ono, Kohsuke Kataoka

{"title":"Glucocorticoids reduce Slc2a2 (GLUT2) gene expression through HNF1 in pancreatic β-cells.","authors":"Yuka Ono, Kohsuke Kataoka","doi":"10.1530/JME-24-0077","DOIUrl":"10.1530/JME-24-0077","url":null,"abstract":"Glucose transporter type 2 (GLUT2), encoded by the Slc2a2 gene, is essential for glucose-stimulated insulin secretion (GSIS) in pancreatic islet β-cells, and low expression of GLUT2 is associated with β-cell dysfunction during the progression of type 2 diabetes in humans and animal models. Glucocorticoids are stress hormones that regulate inflammation and metabolism through the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily, and synthetic glucocorticoids are widely used for the treatment of inflammatory disorders. Prolonged exposure to glucocorticoids induces β-cell dysfunction and diabetes, but the effects of Slc2a2 gene repression in β-cells, if any, and the mechanisms involved remain unclear. In the present study, we measured the expression of GSIS-related genes in the MIN6 β-cell line and found that Slc2a2 mRNA expression was selectively reduced by dexamethasone (DEX), a synthetic glucocorticoid. Using bioinformatics and reporter assays, we identified two β-cell enhancers of the Slc2a2 gene, one within the first intron and another located approximately 40 kb downstream of the transcription start site. The latter enhancer (designated as E3c) was responsible for the DEX-induced repression of the Slc2a2 gene. Of the previously identified β-cell-enriched transcription factors (NEUROD1, MAFA, HNF1α and HNF1β) that activate the E3c enhancer, the transcriptional activity of HNF1α and HNF1β, responsible for maturity-onset diabetes of the young types 3 and 5, respectively, was repressed by DEX and GR. This functional link between HNF1α/HNF1β and GR should help elucidate the mechanism of glucocorticoid-induced β-cell dysfunction and diabetes.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837163","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875080/pdf/","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":"OA","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