Journal of Endocrinology最新文献_第8页

SIRT3 overexpression in rat muscle does not ameliorate peripheral insulin resistance. 大鼠肌肉中SIRT3的过表达并未改善外周胰岛素抵抗。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-09-01 DOI: 10.1530/JOE-22-0101

Brenna Osborne, Lauren E Wright, Amanda E Brandon, Ella Stuart, Lewin Small, Joris Hoeks, Patrick Schrauwen, David A Sinclair, Magdalene K Montgomery, Gregory J Cooney, Nigel Turner

{"title":"SIRT3 overexpression in rat muscle does not ameliorate peripheral insulin resistance.","authors":"Brenna Osborne, Lauren E Wright, Amanda E Brandon, Ella Stuart, Lewin Small, Joris Hoeks, Patrick Schrauwen, David A Sinclair, Magdalene K Montgomery, Gregory J Cooney, Nigel Turner","doi":"10.1530/JOE-22-0101","DOIUrl":"https://doi.org/10.1530/JOE-22-0101","url":null,"abstract":"Reduced expression of the NAD+-dependent deacetylase, SIRT3, has been associated with insulin resistance and metabolic dysfunction in humans and rodents. In this study, we investigated whether specific overexpression of SIRT3 in vivo in skeletal muscle could prevent high-fat diet (HFD)-induced muscle insulin resistance. To address this, we used a muscle-specific adeno-associated virus (AAV) to overexpress SIRT3 in rat tibialis and extensor digitorum longus (EDL) muscles. Mitochondrial substrate oxidation, substrate switching and oxidative enzyme activity were assessed in skeletal muscles with and without SIRT3 overexpression. Muscle-specific insulin action was also assessed by hyperinsulinaemic-euglycaemic clamps in rats that underwent a 4-week HFD-feeding protocol. Ex vivo functional assays revealed elevated activity of selected SIRT3-target enzymes including hexokinase, isocitrate dehydrogenase and pyruvate dehydrogenase that was associated with an increase in the ability to switch between fatty acid- and glucose-derived substrates in muscles with SIRT3 overexpression. However, during the clamp, muscles from rats fed an HFD with increased SIRT3 expression displayed equally impaired glucose uptake and insulin-stimulated glycogen synthesis as the contralateral control muscle. Intramuscular triglyceride content was similarly increased in the muscle of high-fat-fed rats, regardless of SIRT3 status. Thus, despite SIRT3 knockout (KO) mouse models indicating many beneficial metabolic roles for SIRT3, our findings show that muscle-specific overexpression of SIRT3 has only minor effects on the acute development of skeletal muscle insulin resistance in high-fat-fed rats.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"258 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9930786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Neuronal Ptpn1 and Socs3 deletion improves metabolism but not anovulation in a mouse polycystic ovary syndrome model. 在小鼠多囊卵巢综合征模型中，神经元Ptpn1和Socs3缺失可改善代谢，但不能改善无排卵。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-09-01 DOI: 10.1530/JOE-23-0023

Romy I Kerbus, Megan A Inglis, Greg M Anderson

{"title":"Neuronal Ptpn1 and Socs3 deletion improves metabolism but not anovulation in a mouse polycystic ovary syndrome model.","authors":"Romy I Kerbus, Megan A Inglis, Greg M Anderson","doi":"10.1530/JOE-23-0023","DOIUrl":"https://doi.org/10.1530/JOE-23-0023","url":null,"abstract":"Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Approximately half of the diagnosed individuals also experience the metabolic syndrome. Central and peripheral resistance to the hormones insulin and leptin have been reported to contribute to both metabolic and reproductive dysregulation. In PCOS and preclinical PCOS animal models, circulating insulin and leptin levels are often increased in parallel with the development of hormone resistance; however, it remains uncertain whether these changes contribute to the PCOS state. In this study, we tested whether central actions of protein tyrosine phosphatase 1B (PTP1B) and suppressor of cytokine signaling 3 (SOCS3), negative regulators of insulin and leptin signaling pathways, respectively, play a role in the development of PCOS-like phenotype. A peripubertal dihydrotestosterone (DHT) excess PCOS-like mouse model was used, which exhibits both metabolic and reproductive dysfunction. Mice with knockout of the genes encoding PTP1B and SOCS3 from forebrain neurons were generated, and metabolic and reproductive functions were compared between knockout and control groups. DHT treatment induced mild insulin resistance but not leptin resistance, so the role of SOCS3 could not be tested. As expected, DHT excess abolished estrous cycles and corpora lutea presence and caused increased visceral adiposity and fasting glucose levels. Knockout mice did not show any rescue of reproductive dysfunction but did have reduced adiposity compared to the control DHT mice. These data suggest that negative regulation of central insulin signaling by PTP1B is not responsible for peripubertal DHT excess-induced reproductive impairments but may mediate its increased adiposity effects.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"259 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10155901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Blocking FGF23 signaling improves the growth plate of mice with X-linked hypophosphatemia. 阻断FGF23信号通路可改善x连锁低磷血症小鼠的生长。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-09-01 DOI: 10.1530/JOE-23-0025

Rocío Fuente, Eva-Maria Pastor-Arroyo, Nicole Gehring, Patricia Oro Carbajosa, Laura Alonso-Durán, Ivan Zderic, James Tapia-Dean, Ahmad Kamal Hamid, Carla Bettoni, Fernando Santos, Carsten A Wagner, Isabel Rubio-Aliaga

{"title":"Blocking FGF23 signaling improves the growth plate of mice with X-linked hypophosphatemia.","authors":"Rocío Fuente, Eva-Maria Pastor-Arroyo, Nicole Gehring, Patricia Oro Carbajosa, Laura Alonso-Durán, Ivan Zderic, James Tapia-Dean, Ahmad Kamal Hamid, Carla Bettoni, Fernando Santos, Carsten A Wagner, Isabel Rubio-Aliaga","doi":"10.1530/JOE-23-0025","DOIUrl":"https://doi.org/10.1530/JOE-23-0025","url":null,"abstract":"Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone. X-linked hypophosphatemia (XLH) is the most prevalent inherited phosphate wasting disorder due to mutations in the PHEX gene, which cause elevated circulating FGF23 levels. Clinically, it is characterized by growth impairment and defective mineralization of bones and teeth. Treatment of XLH is challenging. Since 2018, neutralizing antibodies against FGF23 have dramatically improved the therapy of XLH patients, although not all patients fully respond to the treatment, and it is very costly. C-terminal fragments of FGF23 have recently emerged as blockers of intact FGF23 signaling. Here, we analyzed the effect on growth and bone of a short 26 residues long C-terminal FGF23 (cFGF23) fragment and two N-acetylated and C-amidated cFGF23 peptides using young XLH mice (Phex C733RMhda mice). Although no major changes in blood parameters were observed after 7 days of treatment with these peptides, bone length and growth plate structure improved. The modified peptides accelerated the growth rate probably by improving growth plate structure and dynamics. The processes of chondrocyte proliferation, death, hypertrophy, and the cartilaginous composition in the growth plate were partially improved in young treated XLH mice. In conclusion, these findings contribute to understand the role of FGF23 signaling in growth plate metabolism and show that this may occur despite continuous hypophosphatemia.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"259 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10332725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Fibroblast growth factor 10 alleviates acute lung injury by inhibiting excessive autophagy via Nrf2. 成纤维细胞生长因子10通过Nrf2抑制过度自噬减轻急性肺损伤。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-09-01 DOI: 10.1530/JOE-23-0095

Shuai Huang, Yincong Xue, Wanying Chen, Mei Xue, Lei Miao, Li Dong, Hao Zuo, Hezhi Wen, Xiong Lei, Zhixiao Xu, Meiyu Quan, Lisha Guo, Yawen Zheng, Zhendong Wang, Li Yang, Yuping Li, Chengshui Chen

{"title":"Fibroblast growth factor 10 alleviates acute lung injury by inhibiting excessive autophagy via Nrf2.","authors":"Shuai Huang, Yincong Xue, Wanying Chen, Mei Xue, Lei Miao, Li Dong, Hao Zuo, Hezhi Wen, Xiong Lei, Zhixiao Xu, Meiyu Quan, Lisha Guo, Yawen Zheng, Zhendong Wang, Li Yang, Yuping Li, Chengshui Chen","doi":"10.1530/JOE-23-0095","DOIUrl":"https://doi.org/10.1530/JOE-23-0095","url":null,"abstract":"Acute lung injury (ALI) is associated with an increased incidence of respiratory diseases, which are devastating clinical disorders with high global mortality and morbidity. Evidence confirms that fibroblast growth factors (FGFs) play key roles in mediating ALI. Mice were treated with LPS (lipopolysaccharide: 5 mg/kg, intratracheally) to establish an in vivo ALI model. Human lung epithelial BEAS-2B cells cultured in a corresponding medium with LPS were used to mimic the ALI model in vitro. In this study, we characterized FGF10 pretreatment (5 mg/kg, intratracheally) which improved LPS-induced ALI, including histopathological changes, and reduced pulmonary edema. At the cellular level, FGF10 pretreatment (10 ng/mL) alleviated LPS-induced ALI accompanied by reduced reactive oxygen species (ROS) accumulation and inflammatory responses, such as IL-1β, IL-6, and IL-10, as well as suppressed excessive autophagy. Additionally, immunoblotting and co-immunoprecipitation showed that FGF10 activated nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway via Nrf2 nuclear translocation by promoting the interaction between p62 and keap1, thereby preventing LPS-induced ALI. Nrf2 knockout significantly reversed these protective effects of FGF10. Together, FGF10 protects against LPS-induced ALI by restraining autophagy via p62-Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 signaling pathway, implying that FGF10 could be a novel therapy for ALI.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"259 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10047244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Neural gut-to-brain communication for postprandial control of satiation and glucose metabolism. 神经肠-脑通讯对餐后饱腹感和葡萄糖代谢的控制。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-09-01 DOI: 10.1530/JOE-22-0320

Leonie Cabot, Juliet Erlenbeck-Dinkelmann, Henning Fenselau

{"title":"Neural gut-to-brain communication for postprandial control of satiation and glucose metabolism.","authors":"Leonie Cabot, Juliet Erlenbeck-Dinkelmann, Henning Fenselau","doi":"10.1530/JOE-22-0320","DOIUrl":"https://doi.org/10.1530/JOE-22-0320","url":null,"abstract":"The brain is tuned to integrate food-derived signals from the gut, allowing it to accurately adjust behavioral and physiological responses in accordance with nutrient availability. A key element of gut-to-brain communication is the relay of neural cues via peripheral sensory neurons (PSN) which harbor functionally specialized peripheral endings innervating the muscular and mucosal layers of gastrointestinal (GI) tract organs. In this review, we detail the properties of GI tract innervating PSN and describe their roles in regulating satiation and glucose metabolism in response to food consumption. We discuss the complex anatomical organization of vagal and spinal PSN subtypes, their peripheral and central projection patterns, and describe the limitations of unselective lesion and ablation approaches to investigate them. We then highlight the recent identification of molecular markers that allow selective targeting of PSN subtypes that innervate GI tract organs. This has facilitated accurately determining their projections, monitoring their responses to gut stimuli, and manipulating their activity. We contend that these recent developments have significantly improved our understanding of PSN-mediated gut-to-brain communication, which may open new therapeutic windows for the treatment of metabolic disorders, such as obesity and type 2 diabetes.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"258 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9937860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Pro-resolving role of glucagon in lipopolysaccharide-induced mice lung neutrophilia. 胰高血糖素在脂多糖诱导小鼠肺中性粒细胞增多症中的促溶解作用。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-09-01 DOI: 10.1530/JOE-22-0196

Daniella Bianchi Reis Insuela, Maximiliano Ruben Ferrero, Amanda da Silva Chaves, Diego de Sá Coutinho, Nathalia Dos Santos Magalhães, Ana Carolina Santos de Arantes, Adriana Ribeiro Silva, Patrícia Machado Rodrigues E Silva, Marco Aurélio Martins, Vinicius Frias Carvalho

{"title":"Pro-resolving role of glucagon in lipopolysaccharide-induced mice lung neutrophilia.","authors":"Daniella Bianchi Reis Insuela, Maximiliano Ruben Ferrero, Amanda da Silva Chaves, Diego de Sá Coutinho, Nathalia Dos Santos Magalhães, Ana Carolina Santos de Arantes, Adriana Ribeiro Silva, Patrícia Machado Rodrigues E Silva, Marco Aurélio Martins, Vinicius Frias Carvalho","doi":"10.1530/JOE-22-0196","DOIUrl":"https://doi.org/10.1530/JOE-22-0196","url":null,"abstract":"Prior research demonstrated that glucagon has protective roles against inflammation, but its effect on the resolution of inflammation remains elusive. Using in vitro and in vivo approaches, this study aimed to investigate the pro-resolving potential of glucagon on pulmonary neutrophilic inflammation caused by lipopolysaccharide. Lipopolysaccharide induced an increase in the proportions of neutrophils positives to glucagon receptor (GcgR) in vitro. In addition, lipopolysaccharide induced an increase in the neutrophil accumulation and expression of GcgR by the inflammatory cells in the lungs, however, without altering glucagon levels. Intranasal treatment with glucagon, at the peak of neutrophilic inflammation, reduced the neutrophil number in the bronchoalveolar lavage (BAL), and lung tissue within 24 h. The reduction of neutrophilic inflammation provoked by glucagon was accompanied by neutrophilia in the blood, an increase in the apoptosis rate of neutrophils in the BAL, enhance in the pro-apoptotic Bax protein expression, and decrease in the anti-apoptotic Bcl-2 protein levels in the lung. Glucagon also induced a rise in the cleavage of caspase-3 in the lungs; however, it was not significant. Glucagon inhibited the levels of IL-1β and TNF-α while increasing the content of pro-resolving mediators transforming growth factor (TGF-β1) and PGE2 in the BAL and lung. Finally, glucagon inhibited lipopolysaccharide-induced airway hyper-reactivity, as evidenced by the reduction in lung elastance values in response to methacholine. In conclusion, glucagon-induced resolution of neutrophilic inflammation by promoting cessation of neutrophil migration and a rise of neutrophil apoptosis and the levels of pro-resolving mediators TGF-β1 and PGE2.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"259 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10285061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Recycling glucocorticoids: therapeutic implications of the 11β-HSD1 enzyme system. 循环糖皮质激素:11β-HSD1酶系统的治疗意义。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-09-01 DOI: 10.1530/JOE-22-0289

Kevin H Tsai, Mark S Cooper

{"title":"Recycling glucocorticoids: therapeutic implications of the 11β-HSD1 enzyme system.","authors":"Kevin H Tsai, Mark S Cooper","doi":"10.1530/JOE-22-0289","DOIUrl":"https://doi.org/10.1530/JOE-22-0289","url":null,"abstract":"Endogenous glucocorticoids and commonly used oral glucocorticoids have the property of existing in an inactive and active form in vivo. The inactive form can be converted back to the active form, or 'recycled' in cells and tissues that express the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. This recycling provides an important contribution to the action of glucocorticoids. This review examines the literature relating to the importance of 11β-HSD1 activity during glucocorticoid treatment, with an emphasis on studies examining bone and joint disease and the ability of glucocorticoids to suppress inflammatory damage in models of arthritis. Animal models with global or selective deletion of 11β-HSD1 have determined the extent to which this recycling is important in normal physiology and during treatment with oral glucocorticoids. These studies demonstrate that 11β-HSD1-mediated recycling of inactive glucocorticoids has a substantial action and indeed is responsible for the majority of the effects of orally administered glucocorticoids on a range of tissues. Importantly, the anti-inflammatory actions of glucocorticoids appear largely through this mechanism such that mice that lack 11β-HSD1 are resistant to the anti-inflammatory actions of glucocorticoids. The recognition that to a large extent the circulating inactive counterpart of these glucocorticoids is more important to anti-inflammatory effects than the active glucocorticoid presents novel opportunities to more selectively target glucocorticoids to tissues or to reduce the likely side effects.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"258 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9914592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Postmenopausal osteoporosis coexisting with sarcopenia: the role and mechanisms of estrogen. 绝经后骨质疏松伴骨骼肌减少症:雌激素的作用及机制。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-09-01 DOI: 10.1530/JOE-23-0116

Lingyun Lu, Li Tian

引用次数: 0

Islet cells in human type 1 diabetes: from recent advances to novel therapies - a symposium-based roadmap for future research. 人类1型糖尿病中的胰岛细胞：从最新进展到新疗法——基于研讨会的未来研究路线图。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-08-31 Print Date: 2023-09-01 DOI: 10.1530/JOE-23-0082

James Cantley, Decio Laks Eizirik, Esther Latres, Colin M Dayan