Journal of Endocrinology最新文献_第9页

Impact of ACE2 on the susceptibility and vulnerability to COVID-19. ACE2对新冠肺炎易感性和易感性的影响。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-08-14 Print Date: 2023-09-01 DOI: 10.1530/JOE-22-0262

Kirsty G Pringle, Lisa K Philp

{"title":"Impact of ACE2 on the susceptibility and vulnerability to COVID-19.","authors":"Kirsty G Pringle, Lisa K Philp","doi":"10.1530/JOE-22-0262","DOIUrl":"10.1530/JOE-22-0262","url":null,"abstract":"Angiotensin-converting enzyme 2 (ACE2) is not only the viral receptor for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but is also classically known as a key carboxypeptidase, which through multiple interacting partners plays vital physiological roles in the heart, kidney, lung, and gastrointestinal tract. An accumulating body of evidence has implicated the dysregulation of ACE2 abundance and activity in the pathophysiology of multiple disease states. ACE2 has recently regained attention due to its evolving role in driving the susceptibility and disease severity of coronavirus disease 2019 (COVID-19). This narrative review outlines the current knowledge of the structure and tissue distribution of ACE2, its role in mediating SARS-CoV-2 cellular entry, its interacting partners, and functions. It also highlights how SARS-CoV-2-mediated dysregulation of membrane-bound and circulating soluble ACE2 during infection plays an important role in the pathogenesis of COVID-19. We explore contemporary evidence for the dysregulation of ACE2 in populations that have emerged as most vulnerable to COVID-19 morbidity and mortality, including the elderly, men, and pregnant women, and draw attention to ACE2 dynamics and discrepancies across the mRNA, protein (membrane-bound and circulating), and activity levels. This review highlights the need for improved understanding of the basic biology of ACE2 in populations vulnerable to COVID-19 to best ensure their clinical management and the appropriate prescription of targeted therapeutics.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"258 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10082031","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

BRD7 improves glucose homeostasis independent of IRS proteins. BRD7独立于IRS蛋白改善葡萄糖稳态。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-08-14 Print Date: 2023-09-01 DOI: 10.1530/JOE-23-0119

Yoo Kim, Junsik M Lee, Youngah Han, Rongya Tao, Morris F White, Renyan Liu, Sang Won Park

{"title":"BRD7 improves glucose homeostasis independent of IRS proteins.","authors":"Yoo Kim, Junsik M Lee, Youngah Han, Rongya Tao, Morris F White, Renyan Liu, Sang Won Park","doi":"10.1530/JOE-23-0119","DOIUrl":"10.1530/JOE-23-0119","url":null,"abstract":"Bromodomain-containing protein 7 (BRD7) has emerged as a player in the regulation of glucose homeostasis. Hepatic BRD7 levels are decreased in obese mice, and the reinstatement of hepatic BRD7 in obese mice has been shown to establish euglycemia and improve glucose homeostasis. Of note, the upregulation of hepatic BRD7 levels activates the AKT cascade in response to insulin without enhancing the sensitivity of the insulin receptor (InsR)-insulin receptor substrate (IRS) axis. In this report, we provide evidence for the existence of an alternative insulin signaling pathway that operates independently of IRS proteins and demonstrate the involvement of BRD7 in this pathway. To investigate the involvement of BRD7 as a downstream component of InsR, we utilized liver-specific InsR knockout mice. Additionally, we employed liver-specific IRS1/2 knockout mice to examine the requirement of IRS1/2 for the action of BRD7. Our investigation of glucose metabolism parameters and insulin signaling unveiled the significance of InsR activation in mediating BRD7's effect on glucose homeostasis in the liver. Moreover, we identified an interaction between BRD7 and InsR. Notably, our findings indicate that IRS1/2 is not necessary for BRD7's regulation of glucose metabolism, particularly in the context of obesity. The upregulation of hepatic BRD7 significantly reduces blood glucose levels and restores glucose homeostasis in high-fat diet-challenged liver-specific IRS1/2 knockout mice. These findings highlight the presence of an alternative insulin signaling pathway that operates independently of IRS1/2 and offer novel insights into the mechanisms of a previously unknown insulin signaling in obesity.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"258 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10430774/pdf/nihms-1922041.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10126507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Hypothalamic neuroendocrine integration of reproduction and metabolism in mammals. 哺乳动物生殖和代谢的下丘脑神经内分泌整合。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-08-10 Print Date: 2023-09-01 DOI: 10.1530/JOE-23-0079

Fan Yang, Shuang Zhao, Pingqing Wang, Wei Xiang

{"title":"Hypothalamic neuroendocrine integration of reproduction and metabolism in mammals.","authors":"Fan Yang, Shuang Zhao, Pingqing Wang, Wei Xiang","doi":"10.1530/JOE-23-0079","DOIUrl":"10.1530/JOE-23-0079","url":null,"abstract":"Reproduction in mammals is an extremely energy-intensive process and is therefore tightly controlled by the body's energy status. Changes in the nutritional status of the body cause fluctuations in the levels of peripheral metabolic hormone signals, such as leptin, insulin, and ghrelin, which provide feedback to the hypothalamus and integrate to coordinate metabolism and fertility. Therefore, to link energy and reproduction, energetic information must be centrally transmitted to gonadotropin-releasing hormone (GnRH) neurons that act as reproductive gating. However, GnRH neurons themselves are rarely directly involved in energy information perception. First, as key factors in the control of GnRH neurons, we describe the direct role of Kisspeptin and Arg-Phe amide-related peptide-3 (RFRP-3) neurons in mediating metabolic signaling. Second, we focused on summarizing the roles of metabolic hormone-sensitive neurons in mediating peripheral energy hormone signaling. Some of these hormone-sensitive neurons can directly transmit energy information to GnRH neurons, such as Orexin neurons, while others act indirectly through other neurons such as Kisspeptin, RFRP-3 neuron, and (pituitary adenylate cyclase-activating polypeptide) PACAP neurons. In addition, as another important aspect of the integration of metabolism and reproduction, the impact of reproductive signaling itself on metabolic function was also considered, as exemplified by our examination of the role of Kisspeptin and RFRP-3 in feeding control. This review summarizes the latest research progress in related fields, in order to more fully understand the central neuropeptide network that integrates energy metabolism and reproduction.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"258 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9974127","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: 2

Sex-specific regulation of prolactin secretion by pituitary activins in postnatal development. 产后发育中垂体激活素对泌乳素分泌的性别特异性调节。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-08-02 Print Date: 2023-09-01 DOI: 10.1530/JOE-23-0020

Alejandra Abeledo Machado, Dana Bornancini, Milagros Peña-Zanoni, María Andrea Camilletti, Erika Yanil Faraoni, Graciela Diaz-Torga

{"title":"Sex-specific regulation of prolactin secretion by pituitary activins in postnatal development.","authors":"Alejandra Abeledo Machado, Dana Bornancini, Milagros Peña-Zanoni, María Andrea Camilletti, Erika Yanil Faraoni, Graciela Diaz-Torga","doi":"10.1530/JOE-23-0020","DOIUrl":"10.1530/JOE-23-0020","url":null,"abstract":"Serum prolactin increases from birth to adulthood in rats, being higher in females from birth. The maturation of hypothalamic/gonadal prolactin-releasing and -inhibiting factors does not explain some sex differences observed. During the first weeks of life, prolactin secretion increases, even when lactotrophs are isolated in vitro, in the absence of those controls, suggesting the participation of intra-pituitary factors in this control. The present work aimed to study the involvement of pituitary activins in the regulation of prolactin secretion during post-natal development. Sex differences were also highlighted. Female and male Sprague-Dawley rats at 11, 23 and 45postnatal days were used. Pituitary expression of activin subunits and activin receptors was maximum in p11 female pituitaries, being even higher than that observed in males. Those expressions decrease with age in females, and then the gender differences disappear at p23. Inhbb expression strongly increases at p45 in males, being the predominant subunit in this sex in adulthood. Activin inhibition of prolactin is mediated by the inhibition of Pit-1 expression. This action involves not only the canonical pSMAD pathway but also the phosphorylation of p38MAPK. At p11, almost all lactotrophs express p-p38MAPK in females, and its expression decreases with age with a concomitant increase in Pit-1. Our findings suggest that the inhibitory regulation of pituitary activins on prolactin secretion is sex specific; this regulation is more relevant in females during the first week of life and decreases with age; this intra-pituitary regulation is involved in the sex differences observed in serum prolactin levels during postnatal development.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"258 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10294552","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: 1

α-cell electrophysiology and the regulation of glucagon secretion. α-细胞电生理与胰高血糖素分泌的调节。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-08-01 DOI: 10.1530/JOE-22-0295

Rui Gao, Samuel Acreman, Jinfang Ma, Fernando Abdulkader, Anna Wendt, Quan Zhang

{"title":"α-cell electrophysiology and the regulation of glucagon secretion.","authors":"Rui Gao, Samuel Acreman, Jinfang Ma, Fernando Abdulkader, Anna Wendt, Quan Zhang","doi":"10.1530/JOE-22-0295","DOIUrl":"https://doi.org/10.1530/JOE-22-0295","url":null,"abstract":"Glucagon is the principal glucose-elevating hormone that forms the first-line defence against hypoglycaemia. Along with insulin, glucagon also plays a key role in maintaining systemic glucose homeostasis. The cells that secrete glucagon, pancreatic α-cells, are electrically excitable cells and use electrical activity to couple its hormone secretion to changes in ambient glucose levels. Exactly how glucose regulates α-cells has been a topic of debate for decades but it is clear that electrical signals generated by the cells play an important role in glucagon secretory response. Decades of studies have already revealed the key players involved in the generation of these electrical signals and possible mechanisms controlling them to tune glucagon release. This has offered the opportunity to fully understand the enigmatic α-cell physiology. In this review, we describe the current knowledge on cellular electrophysiology and factors regulating excitability, glucose sensing, and glucagon secretion. We also discuss α-cell pathophysiology and the perspective of addressing glucagon secretory defects in diabetes for developing better diabetes treatment, which bears the hope of eliminating hypoglycaemia as a clinical problem in diabetes care.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"258 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10121708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Mineralocorticoid receptor knockout in Schwann cells alters myelin sheath thickness. 雪旺细胞中矿化皮质激素受体敲除改变髓鞘厚度。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-08-01 DOI: 10.1530/JOE-22-0334

Alberto González-Mayoral, Axel Eid, Razmig Derounian, Virginia Sofia Campanella, Andreia da Silva Ramos, Romy El Khoury, Charbel Massaad, Damien Le Menuet

{"title":"Mineralocorticoid receptor knockout in Schwann cells alters myelin sheath thickness.","authors":"Alberto González-Mayoral, Axel Eid, Razmig Derounian, Virginia Sofia Campanella, Andreia da Silva Ramos, Romy El Khoury, Charbel Massaad, Damien Le Menuet","doi":"10.1530/JOE-22-0334","DOIUrl":"https://doi.org/10.1530/JOE-22-0334","url":null,"abstract":"Myelination allows fast and synchronized nerve influxes and is provided by Schwann cells (SCs) in the peripheral nervous system. Glucocorticoid hormones are major regulators of stress, metabolism and immunity affecting all tissues. They act by binding to two receptors, the low-affinity glucocorticoid receptor (GR) and the high-affinity mineralocorticoid receptor (MR). Little is known about the effect of glucocorticoid hormones on the PNS, and this study focuses on deciphering the role of MR in peripheral myelination. In this work, the presence of a functional MR in SCs is demonstrated and the expression of MR protein in mouse sciatic nerve SC is evidenced. Besides, knockout of MR in SC (SCMRKO using Cre-lox system with DesertHedgeHog (Dhh) Cre promoter) was undertaken in mice. SCMRKO was not associated with alterations of performance in motor behavioral tests on 2- to 6-month-old male mice compared to their controls. No obvious modifications of myelin gene expression or MR signaling gene expression were observed in the SCMRKO sciatic nerves. Nevertheless, Gr transcript and GR protein amounts were significantly increased in SCMRKO nerves compared to controls, suggesting a possible compensatory effect. Besides, an increase in myelin sheath thickness was noted for axons with perimeters larger than 15 µm in SCMRKO illustrated by a significant 4.5% reduction in g-ratio (axon perimeter/myelin sheath perimeter). Thus, we defined MR as a new player in peripheral system myelination and in SC homeostasis.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"258 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9790715","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

The alternate pathway of androgen metabolism and window of sensitivity. 雄激素代谢的替代途径和敏感性窗口。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-08-01 Print Date: 2023-09-01 DOI: 10.1530/JOE-22-0296

Marilyn B Renfree, Geoff Shaw

{"title":"The alternate pathway of androgen metabolism and window of sensitivity.","authors":"Marilyn B Renfree, Geoff Shaw","doi":"10.1530/JOE-22-0296","DOIUrl":"10.1530/JOE-22-0296","url":null,"abstract":"Since the discovery in 1968 that dihydrotestosterone (DHT) is a major mediator of androgen action, a convincing body of evidence has accumulated to indicate that the major pathway of DHT formation is the 5α-reduction of circulating testosterone in androgen target tissues. However, we now know that DHT can also be formed in peripheral tissues by the oxidation of 5α-androstane-3α,17β-diol (adiol). This pathway is responsible for the formation of the male phenotype. We discuss the serendipitous discovery in the tammar wallaby of an alternate pathway by which adiol is formed in the testes, secreted into plasma and converted in peripheral tissues to DHT. This alternate pathway is responsible for virilisation of the urogenital system in this species and is present in the testes at the onset of male puberty of all mammals studied so far. This is the first clear-cut function for steroid 5α-reductase 1 in males. Unexpectedly, the discovery of this pathway in this Australian marsupial has had a major impact in understanding the pathophysiology of aberrant virilisation in female newborns. Overactivity of the alternate pathway appears to explain virilisation in congenital adrenal hyperplasia CAH, in X-linked 46,XY disorders of sex development. It also appears to be important in polycystic ovarian syndrome (PCOS) since PCOS ovaries have enhanced the expression of genes and proteins of the alternate pathway. It is now clear that normal male development in marsupials, rodents and humans requires the action of both the classic and the alternate (backdoor) pathways.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"258 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9926204","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

Brief overview: glucagon history and physiology. 简要概述:胰高血糖素的历史和生理。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-08-01 DOI: 10.1530/JOE-22-0224

R Paul Robertson

{"title":"Brief overview: glucagon history and physiology.","authors":"R Paul Robertson","doi":"10.1530/JOE-22-0224","DOIUrl":"https://doi.org/10.1530/JOE-22-0224","url":null,"abstract":"Glucagon is a peptide hormone that is produced primarily by the alpha cells in the islet of Langerhans in the pancreas, but also in intestinal enteroendocrine cells and in some neurons. Approximately 100 years ago, several research groups discovered that pancreatic extracts would cause a brief rise in blood glucose before they observed the decrease in glucose attributed to insulin. An overall description of the regulation of glucagon secretion requires the inclusion of its sibling insulin because they both are made primarily by the islet and they both regulate each other in different ways. For example, glucagon stimulates insulin secretion, whereas insulin suppresses glucagon secretion. The mechanism of action of glucagon on insulin secretion has been identified as a trimeric guanine nucleotide-binding protein (G-protein)-mediated event. The manner in which insulin suppresses glucagon release from the alpha cell is thought to be highly dependent on the peri-portal circulation of the islet through which blood flows downstream from beta cells to alpha cells. In this scenario, it is via the circulation that insulin is thought to suppress the release of glucagon. However, high levels of glucose also have been shown to suppress glucagon secretion. Consequently, the glucose-lowering effect of insulin may be additive to the direct effects of insulin to suppress alpha cell function, so that in vivo both the discontinuation of the insulin signal and the condition of low glucose jointly are responsible for induction of glucagon secretion.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"258 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797283","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: 1

Intercellular contacts affect secretion and biosynthesis of pancreatic islet cells. 细胞间接触影响胰岛细胞的分泌和生物合成。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-08-01 DOI: 10.1530/JOE-22-0304

David Cottet-Dumoulin, Quentin Perrier, Vanessa Lavallard, David Matthey-Doret, Laura Mar Fonseca, Juliette Bignard, Reine Hanna, Geraldine Parnaud, Fanny Lebreton, Kevin Bellofatto, Ekaterine Berishvili, Thierry Berney, Domenico Bosco

{"title":"Intercellular contacts affect secretion and biosynthesis of pancreatic islet cells.","authors":"David Cottet-Dumoulin, Quentin Perrier, Vanessa Lavallard, David Matthey-Doret, Laura Mar Fonseca, Juliette Bignard, Reine Hanna, Geraldine Parnaud, Fanny Lebreton, Kevin Bellofatto, Ekaterine Berishvili, Thierry Berney, Domenico Bosco","doi":"10.1530/JOE-22-0304","DOIUrl":"https://doi.org/10.1530/JOE-22-0304","url":null,"abstract":"Cell protein biosynthesis is regulated by different factors, but implication of intercellular contacts on alpha and beta cell protein biosyntheses activity has not been yet investigated. Islet cell biosynthetic activity is essential in regulating not only the hormonal reserve within cells but also in renewing all the proteins involved in the control of secretion. Here we aimed to assess whether intercellular interactions affected similarly secretion and protein biosynthesis of rat alpha and beta cells. Insulin and glucagon secretion were analyzed by ELISA or reverse hemolytic plaque assay, and protein biosynthesis evaluated at single cell level using bioorthogonal noncanonical amino acid tagging. Regarding beta cells, we showed a positive correlation between insulin secretion and protein biosynthesis. We also observed that homologous contacts increased both activities at low or moderate glucose concentrations. By contrast, at high glucose concentration, homologous contacts increased insulin secretion and not protein biosynthesis. In addition, heterogeneous contacts between beta and alpha cells had no impact on insulin secretion and protein biosynthesis. Regarding alpha cells, we showed that when they were in contact with beta cells, they increased their glucagon secretion in response to a drop of glucose concentration, but, on the other hand, they decreased their protein biosynthesis under any glucose concentrations. Altogether, these results emphasize the role of intercellular contacts on the function of islet cells, showing that intercellular contacts increased protein biosynthesis in beta cells, except at high glucose, and decreased protein biosynthesis in alpha cells even when glucagon secretion is stimulated.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"258 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10153357","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

Testosterone and type 2 diabetes prevention: translational lessons from the T4DM study. 睾酮与2型糖尿病预防：T4DM研究的转化经验教训。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2023-08-01 Print Date: 2023-09-01 DOI: 10.1530/JOE-22-0223

Gary A Wittert, Mathis Grossmann, Bu B Yeap, David J Handelsman

{"title":"Testosterone and type 2 diabetes prevention: translational lessons from the T4DM study.","authors":"Gary A Wittert, Mathis Grossmann, Bu B Yeap, David J Handelsman","doi":"10.1530/JOE-22-0223","DOIUrl":"10.1530/JOE-22-0223","url":null,"abstract":"Testosterone acting via the androgen receptor, and via aromatisation to oestradiol, an activator of the oestrogen receptor, plays key roles in adipose tissue, bone and skeletal muscle biology. This is reflected in epidemiological studies associating obesity and disordered glucose metabolism with lower serum testosterone concentrations and an increased risk of type 2 diabetes (T2D) in men. Testosterone also modulates erythrocytosis and vascular endothelial and smooth muscle cell function, with potential impacts on haematocrit and the cardiovascular system. The Testosterone for the Prevention of Type 2 Diabetes (T4DM) study enrolled men aged 50 years and over with a waist circumference of 95 cm or over, impaired glucose tolerance or newly diagnosed T2D, and a serum testosterone concentration (as measured by chemiluminescence immunoassay) <14.0 nmol/L. The study reported that a 2-year treatment with testosterone undecanoate 1000 mg, administered 3-monthly intramuscularly, on the background of a lifestyle program, reduced the likelihood of T2D diagnosis by 40% compared to placebo. This effect was accompanied by a decrease in fasting serum glucose and associated with favourable changes in body composition, hand grip strength, bone mineral density and skeletal microarchitecture but not in HbA1c, a red blood cell-dependent measure of glycaemic control. There was no signal for cardiovascular adverse events. With the objective of informing translational science and future directions, this article discusses mechanistic studies underpinning the rationale for T4DM and translational implications of the key outcomes relating to glycaemia, and body composition, together with effects on erythrocytosis, cardiovascular risk and slow recovery of the hypothalamo-pituitary-testicular axis.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"258 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9900932","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