Journal of Endocrinology最新文献_第10页

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-04-01 DOI: 10.1530/joe-23-0377

Se-Min Kim, Farthath Sultana, Steven Sims, Judit Gimenez-Roig, Victoria Laurencin, Anusha Pallapati, Satish Rojekar, Vitaly Ryu, Daria Lizneva, Funda Korkmaz, Tony Yuen, Mone Zaidi

{"title":"FSH, bone, belly and brain","authors":"Se-Min Kim, Farthath Sultana, Steven Sims, Judit Gimenez-Roig, Victoria Laurencin, Anusha Pallapati, Satish Rojekar, Vitaly Ryu, Daria Lizneva, Funda Korkmaz, Tony Yuen, Mone Zaidi","doi":"10.1530/joe-23-0377","DOIUrl":"https://doi.org/10.1530/joe-23-0377","url":null,"abstract":"The pituitary gland, often called the “master gland”, orchestrates multiple effector hormonal organs and other glands by secreting various tropic hormones, which play a significant role in a myriad of physiological processes including skeletal modeling and remodeling, fat and glucose metabolism, and cognitive and psychological processes. The findings of the expression of receptors for each pituitary hormone and the hormone itself in skeleton, fat and immune cells suggested that their role is much broader than the traditional or classic role. Follicle-stimulating hormone (FSH), once believed to regulate gonadal function – gonadal development and maturation at puberty and gamete production during the fertile phase – is also found to involve in fat and bone metabolism as well as cognition, which provides us a better understanding of complex physiology. This emerging understanding of the non-reproductive role of FSH opens potential therapeutic opportunity to address detrimental health burden during and after menopause, namely osteoporosis, obesity and dementia. In this Review, we outline the current understanding of crosstalk between the pituitary, bone, adipose tissue and brain through FSH. The pre-clinical evidence from genetic and pharmacologic intervention in rodent models, and human data from population-based observation, genetic studies, and a small number of studies with interventional nature support an independent skeletal, lipogenic and cognitive effect of FSH and more.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"105 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586125","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

Glucagon resistance and metabolic-associated steatotic liver disease: a review of the evidence 胰高血糖素抵抗与代谢相关性脂肪肝：证据综述

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-04-01 DOI: 10.1530/joe-23-0365

Emma Rose McGlone, Steve R Bloom, Tricia Mei-Mei Tan

{"title":"Glucagon resistance and metabolic-associated steatotic liver disease: a review of the evidence","authors":"Emma Rose McGlone, Steve R Bloom, Tricia Mei-Mei Tan","doi":"10.1530/joe-23-0365","DOIUrl":"https://doi.org/10.1530/joe-23-0365","url":null,"abstract":"Metabolic-associated steatotic liver disease (MASLD) is closely associated with obesity. MASLD affects over one billion adults globally but there are few treatment options available. Glucagon is a key metabolic regulator, and its actions include the reduction of liver fat through direct and indirect means. Chronic glucagon signalling deficiency is associated with hyperaminoacidaemia, hyperglucagonaemia, and increased circulating levels of glucagon-like peptide 1 (GLP-1) and fibroblast growth factor-21 (FGF-21). Reduction in glucagon activity decreases hepatic amino acid and triglyceride catabolism; metabolic effects include improved glucose tolerance, increased plasma cholesterol and increased liver fat. Conversely, glucagon infusion in healthy volunteers leads to increased hepatic glucose output, decreased levels of plasma amino acids and increased urea production, decreased plasma cholesterol and increased energy expenditure. Patients with MASLD share many hormonal and metabolic characteristics with models of glucagon signalling deficiency, suggesting that they could be resistant to glucagon. Although there are few studies of the effects of glucagon infusion in patients with obesity and/or MASLD, there is some evidence that the expected effect of glucagon on amino acid catabolism may be attenuated. Taken together, this evidence supports the notions that glucagon resistance exists in patients with MASLD and may contribute to the pathogenesis of MASLD. Further studies are warranted to investigate the direct effects of glucagon on metabolism in patients with MASLD.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"79 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586145","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 interplay of glucose-dependent insulinotropic polypeptide in adipose tissue 脂肪组织中葡萄糖依赖性促胰岛素多肽的相互作用

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-04-01 DOI: 10.1530/joe-23-0361

Samrin Kagdi, Sulayman Lyons, Jacqueline L Beaudry

{"title":"The interplay of glucose-dependent insulinotropic polypeptide in adipose tissue","authors":"Samrin Kagdi, Sulayman Lyons, Jacqueline L Beaudry","doi":"10.1530/joe-23-0361","DOIUrl":"https://doi.org/10.1530/joe-23-0361","url":null,"abstract":"Adipose tissue was once known as a reservoir for energy storage but is now considered a crucial organ for hormone and energy flux with important effects on health and disease. Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted from the small intestinal K-cells, responsible for augmenting insulin release, and has gained attention for its independent and amicable effects with glucagon-like peptide-1 (GLP-1), another incretin hormone secreted from the small intestinal L-cells. The GIP receptor (GIPR) is found in whole adipose tissue, whereas the GLP-1 receptor (GLP-1R) is not, and some studies suggest that GIPR action lowers body weight and plays a role in lipolysis, glucose/lipid uptake/disposal, adipose tissue blood flow, lipid oxidation, and free-fatty acid (FFA) re-esterification that may or may not be influenced by other hormones such as insulin. This review summarizes the research on the effects of GIP in adipose tissue (distinct depots of white and brown) using cellular, rodent, and human models. In doing so, we explore the mechanisms of GIPR-based medications for treating metabolic disorders, such as type 2 diabetes and obesity, and how GIPR agonism and antagonism contribute to improvements in metabolic health outcomes, potentially through actions in adipose tissues.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"52 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586050","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

Androgens and immune cell function 雄激素与免疫细胞功能

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-04-01 DOI: 10.1530/joe-23-0398

Rebecca J Ainslie, Ioannis Simitsidellis, Phoebe M Kirkwood, Douglas A Gibson

{"title":"Androgens and immune cell function","authors":"Rebecca J Ainslie, Ioannis Simitsidellis, Phoebe M Kirkwood, Douglas A Gibson","doi":"10.1530/joe-23-0398","DOIUrl":"https://doi.org/10.1530/joe-23-0398","url":null,"abstract":"Androgens can modulate immune cell function and may contribute to differences in the prevalence and severity of common inflammatory conditions. Although most immune cells are androgen targets, our understanding of how changes in androgen bioavailability can affect immune responses is incomplete. Androgens alter immune cell composition, phenotype and activation by modulating expression and secretion of inflammatory mediators or by altering development and maturation of immune cell precursors. Androgens are generally associated with having suppressive effects on the immune system but their impacts are cell and tissue context dependent and can be highly nuanced even within immune cell subsets. In response to androgens, innate immune cells such as neutrophils, monocytes, and macrophages increase production of the anti-inflammatory cytokine IL10 and decrease nitric oxide production. Androgens promote differentiation of T cell subsets and reduce production of inflammatory mediators, such as IFNG, IL4 and IL5. Additionally, androgens/AR can promote maturation of B cells. Thus, androgens can be considered as immunomodulatory agents but further work is required to understand the precise molecular pathways that are regulated at the intersection between endocrine and inflammatory signals. This narrative review focusses on summarising our current understanding of how androgens can alter immune cell function and how this might affect inflammatory responses in health and disease.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"53 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586301","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

Consistent and effective method to define the mouse estrous cycle stage by deep learning based model 通过基于深度学习的模型确定小鼠发情周期阶段的一致有效方法

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-04-01 DOI: 10.1530/joe-23-0204

Leena Strauss, Arttu Junnila, Anni Wärri, Maria Manti, Yiwen Jiang, Eliisa Löyttyniemi, Elisabet Stener-Victorin, Marie K Lagerquist, Krisztina Kukoricza, Taija Heinosalo, Sami Blom, Matti Poutanen

{"title":"Consistent and effective method to define the mouse estrous cycle stage by deep learning based model","authors":"Leena Strauss, Arttu Junnila, Anni Wärri, Maria Manti, Yiwen Jiang, Eliisa Löyttyniemi, Elisabet Stener-Victorin, Marie K Lagerquist, Krisztina Kukoricza, Taija Heinosalo, Sami Blom, Matti Poutanen","doi":"10.1530/joe-23-0204","DOIUrl":"https://doi.org/10.1530/joe-23-0204","url":null,"abstract":"The mouse estrous cycle is divided into four stages: proestrus (P), estrus (E), metestrus (M) and diestrus (D). The estrous cycle affects reproductive hormone levels in a wide variety of tissues. Therefore, to obtain reliable results from female mice, it is important to know the estrous cycle stage during sampling. The stage can be analyzed from a vaginal smear under a microscope. However, it is time-consuming, and the results vary between evaluators. Here, we present an accurate and reproducible method for staging the mouse estrous cycle in digital whole slide images (WSIs) of vaginal smears. We developed a model using a deep convolutional neural network (CNN) in a cloud-based platform, Aiforia Create. The CNN was trained by supervised pixel-level multiclass semantic segmentation of image features from 171 hematoxylin-stained samples. The model was validated by comparing the results obtained by CNN with those of four independent researchers. The validation data included three separate studies comprising altogether 148 slides. The total agreement attested by the Fleiss kappa value between the validators and the CNN was excellent (0.75), and when D, E and P were analyzed separately, the kappa values were 0.89, 0.79 and 0.74, respectively. The M stage is short and not well defined by the researchers. Thus, identification of the M stage by the CNN was challenging due to the lack of proper ground truth, and the kappa value was 0.26. We conclude that our model is reliable and effective for classifying the estrous cycle stages in female mice.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"301 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140602408","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 emerging role of glucagon-like peptide-1 in binge eating 胰高血糖素样肽-1 在暴食中的新作用

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-04-01 DOI: 10.1530/joe-23-0405

Katherine N. Balantekin, Martin J. Kretz, Elizabeth G Mietlicki-Baase

{"title":"The emerging role of glucagon-like peptide-1 in binge eating","authors":"Katherine N. Balantekin, Martin J. Kretz, Elizabeth G Mietlicki-Baase","doi":"10.1530/joe-23-0405","DOIUrl":"https://doi.org/10.1530/joe-23-0405","url":null,"abstract":"Binge eating is a central component of two clinical eating disorders, binge eating disorder and bulimia nervosa, but the large treatment gap highlights the need to identify other strategies to decrease binge eating. Novel pharmacotherapies may be one such approach. Glucagon-like peptide-1 (GLP-1) is an intestinal and brain-derived neuroendocrine signal with a critical role in promoting glycemic control through its incretin effect. Additionally, the energy balance effects of GLP-1 are well-established; activation of the GLP-1 receptor (GLP-1R) reduces food intake and body weight. Aligned with these beneficial metabolic effects, there are GLP-1R agonists that are currently used for the treatment of diabetes and obesity. A growing body of literature suggests that GLP-1 may also play an important role in binge eating. Dysregulation of the endogenous GLP-1 system is associated with binge eating in non-human animal models, and GLP-1R agonists may be a promising approach to suppress the overconsumption that occurs during binge eating. Here, we briefly discuss the role of GLP-1 in normal energy intake and reward, and then review the emerging evidence suggesting that disruptions to GLP-1 signaling are associated with binge eating. We also consider the potential utility of GLP-1-based pharmacotherapies for reducing binge eating behavior.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"58 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140615499","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

An adipocentric perspective of pancreatic lipotoxicity in diabetes pathogenesis 从脂肪中心角度看糖尿病发病机制中的胰腺脂肪毒性

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-04-01 DOI: 10.1530/joe-23-0313

Renata Risi, Antonio J Vidal-Puig, Guillaume Bidault

{"title":"An adipocentric perspective of pancreatic lipotoxicity in diabetes pathogenesis","authors":"Renata Risi, Antonio J Vidal-Puig, Guillaume Bidault","doi":"10.1530/joe-23-0313","DOIUrl":"https://doi.org/10.1530/joe-23-0313","url":null,"abstract":"Obesity and diabetes represent two increasing and invalidating public health issues that often coexist. It is acknowledged that fat mass excess predisposes to insulin resistance and type 2 diabetes mellitus (T2D), with the increasing incidence of the two diseases significantly associated. Moreover, emerging evidence suggests that obesity might also accelerate the appearance of type 1 diabetes (T1D), which is now a relatively frequent comorbidity in patients with obesity. It is a common clinical finding that not all patients with obesity will develop diabetes at the same level of adiposity, with gender, genetic, and ethnic factors playing an important role in defining the timing of diabetes appearance. The adipose tissue (AT) expandability hypothesis explains this paradigm, indicating that the individual capacity to appropriately store energy surplus in the form of fat within the AT determines and prevents the toxic deposition of lipids in other organs, such as the pancreas. Thus, we posit that when the maximal storing capacity of AT is exceeded, individuals will develop T2D. In this review, we provide an insight into mechanisms by which the AT controls pancreas lipid content and homeostasis in case of obesity to offer an adipocentric perspective of pancreatic lipotoxicity in the pathogenesis of diabetes. Moreover, we suggest that improving AT function is a valid therapeutic approach to fighting obesity-associated complications including diabetes.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"8 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140615551","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 glucocorticoid receptor in skeletal health and disease: insights from targeted knockout mice. 骨骼健康和疾病中的糖皮质激素受体：靶向基因敲除小鼠的启示

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-03-28 Print Date: 2024-05-01 DOI: 10.1530/JOE-23-0399

Eugenie Macfarlane, Hong Zhou, Markus J Seibel

{"title":"The glucocorticoid receptor in skeletal health and disease: insights from targeted knockout mice.","authors":"Eugenie Macfarlane, Hong Zhou, Markus J Seibel","doi":"10.1530/JOE-23-0399","DOIUrl":"10.1530/JOE-23-0399","url":null,"abstract":"Glucocorticoids are steroid hormones, secreted by the adrenals to regulate a range of metabolic, immunologic, and homeostatic functions. Due to their potent anti-inflammatory effects, synthetic glucocorticoids are widely used to treat inflammatory disorders. However, their use especially at high doses and over the long-term is associated with several unwanted side effects that compromises their intended use (e.g. glucocorticoid-induced osteoporosis and/or diabetes, myopathy, and skin atrophy). Both endogenous and synthetic glucocorticoids exert their effects through the glucocorticoid receptor, a transcription factor present in nearly all nucleated cells. Glucocorticoid receptor knockout mouse models have proved to be valuable tools in understanding how glucocorticoids contribute to skeletal health and disease. These models, described in this review, have helped to establish that the effects of glucocorticoids on the skeleton are multifaceted, cell specific and concentration dependent. Intriguingly, while endogenous glucocorticoids are essential for bone formation, high-dose exogenous glucocorticoids may induce bone loss. Additionally, the actions of endogenous glucocorticoids vary greatly depending on the disease microenvironment. For example, endogenous glucocorticoids have predominately beneficial anti-inflammatory effects in rheumatoid arthritis, but detrimental actions in osteoarthritis by driving cartilage loss and abnormal bone formation. Studies in tissue-specific knockout models provide important insights that will aid the development of new glucocorticoid therapeutics that can specifically target certain cell types to minimise unwanted effects from current glucocorticoid therapy.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140059573","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

Microbiome dysbiosis by antibiotics protects cartilage degradation in OAOP mice. 抗生素造成的微生物群失调保护了 OAOP 小鼠的软骨退化。

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-03-13 Print Date: 2024-05-01 DOI: 10.1530/JOE-23-0330

Qin Yin, Jun Gu, Pengju Ren, Zhiqiang Guan, Yongxiang Wang, Ruijun Bai, Yu Liu

{"title":"Microbiome dysbiosis by antibiotics protects cartilage degradation in OAOP mice.","authors":"Qin Yin, Jun Gu, Pengju Ren, Zhiqiang Guan, Yongxiang Wang, Ruijun Bai, Yu Liu","doi":"10.1530/JOE-23-0330","DOIUrl":"10.1530/JOE-23-0330","url":null,"abstract":"The role of this study was to evaluate the impact of gut microbiota depletion on the progression of osteoarthritis (OA) and osteoporosis (OP). We conducted an experimental mouse model of OA and OP over an 8-week period. The model involved destabilization of the medial meniscus and bilateral ovariectomy (OVX). To deplete the gut microbiota, we administered a course of antibiotics for 8 weeks. The severity of OA was assessed through micro-CT scanning, X-rays, and immunohistochemical staining. Microbiome analysis was performed using PCR of 16S DNA on fecal samples, and the levels of serum lipopolysaccharide, interleukin 6, tumor necrosis factor-α (TNF-α), osteocalcin, and estrogen were measured using enzyme-linked immunosorbent assay. We found that in comparison to the OVX+OA group, the OVX+OA+ABT group exhibited increased bone mineral density (P < 0.0001), bone volume fraction (P = 0.0051), and trabecular number (P = 0.0023) in the metaphyseal bone. Additionally, cartilage injury and levels of matrix metalloproteinase 13 were reduced in the OVX+OA+ABT group compared to the OVX+OA group. Moreover, the OVX+OA+ABT group demonstrated decreased relative abundance of Bacteroidetes, serum lipopolysaccharide (P = 0.0005), TNF-α (P < 0.0001), CTX-1 (P = 0.0002), and increased expression of bone formation markers. These findings were further supported by correlation network analyses. Depletion of gut microbiota was shown to protect against bone loss and cartilage degradation by modulating the composition of the gut microbiota in osteoporosis and osteoarthritis.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542364","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

Insulin induces bioenergetic changes and alters mitochondrial dynamics in podocytes 胰岛素诱导生物能变化并改变荚膜细胞中线粒体的动态变化

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-03-01 DOI: 10.1530/joe-23-0357

Irena Audzeyenka, Patrycja Rachubik, Dorota Rogacka, Moin A Saleem, Agnieszka Piwkowska

{"title":"Insulin induces bioenergetic changes and alters mitochondrial dynamics in podocytes","authors":"Irena Audzeyenka, Patrycja Rachubik, Dorota Rogacka, Moin A Saleem, Agnieszka Piwkowska","doi":"10.1530/joe-23-0357","DOIUrl":"https://doi.org/10.1530/joe-23-0357","url":null,"abstract":"Diabetic nephropathy (DN) is one of the most frequent complications of diabetes. Early stages of DN are associated with hyperinsulinemia and progressive insulin resistance in insulin-sensitive cells, including podocytes. The diabetic environment induces pathological changes, especially in podocyte bioenergetics, which is tightly linked with mitochondrial dynamics. The regulatory role of insulin in mitochondrial morphology in podocytes has not been fully elucidated. Therefore, the main goal of the present study was to investigate effects of insulin on the regulation of mitochondrial dynamics and bioenergetics in human podocytes. Biochemical analyses were performed to assess oxidative phosphorylation efficiency by measuring the oxygen consumption rate (OCR) and glycolysis by measuring the extracellular acidification rate (ECAR). mRNA and protein expression were determined by real-time polymerase chain reaction and Western blot. The intracellular mitochondrial network was visualized by MitoTracker staining. All calculations were conducted using CellProfiler software. Short-term insulin exposure exerted inhibitory effects on various parameters of oxidative respiration and adenosine triphosphate production, and glycolysis flux was elevated. After a longer time of treating cells with insulin, an increase in mitochondrial size was observed, accompanied by a reduction of expression of the mitochondrial fission markers DRP1 and FIS1 and an increase in mitophagy. Overall, we identified a previously unknown role for insulin in the regulation of oxidative respiration and glycolysis and elucidated mitochondrial dynamics in human podocytes. The present results emphasize the importance of the duration of insulin stimulation for its metabolic and molecular effects, which should be considered in clinical and experimental studies of DN.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"9 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140324745","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