Journal of Endocrinology最新文献_第5页

Lipid regulation of the glucagon receptor family 胰高血糖素受体家族的脂质调节

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-04-01 DOI: 10.1530/joe-23-0335

Affiong Ika Oqua, Yusman Manchanda, Emma Rose McGlone, Ben Jones, Sarah Rouse, Alejandra Tomas

{"title":"Lipid regulation of the glucagon receptor family","authors":"Affiong Ika Oqua, Yusman Manchanda, Emma Rose McGlone, Ben Jones, Sarah Rouse, Alejandra Tomas","doi":"10.1530/joe-23-0335","DOIUrl":"https://doi.org/10.1530/joe-23-0335","url":null,"abstract":"The glucagon receptor family are typical class B1 G protein-coupled receptors (GPCRs) with important roles in metabolism, including the control of pancreas, brain, and liver function. As proteins with 7 transmembrane domains, GPCRs are intimately in contact with lipid bilayers and therefore can be putatively regulated by interactions with their lipidic components, including cholesterol, sphingolipids, and other lipid species. Additionally, these receptors, as well as the agonists they bind to, can undergo lipid modifications, which can influence their binding capacity and/or elicit modified or biased signalling profiles. While the effect of lipids, and in particular cholesterol, has been widely studied for other GPCR classes, information about their role in regulating the glucagon receptor family is only beginning to emerge. Here we summarise our current knowledge on the effects of cholesterol modulation of glucagon receptor family signalling and trafficking profiles, as well as existing evidence for specific lipid–receptor binding and indirect effects of lipids via lipid modification of cognate agonists. Finally, we discuss the different methodologies that can be employed to study lipid-receptor interactions and summarise the importance of this area of investigation to increase our understanding of the biology of this family of metabolically relevant receptors.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586133","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

Glyphosate-based herbicide worsens alterations induced by cafeteria diet on rat uterus 草甘膦除草剂会加剧食堂饮食对大鼠子宫造成的改变

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-04-01 DOI: 10.1530/joe-24-0071

María Victoria Zanardi, María Paula Gastiazoro, María F. Rossetti, Florencia Doná, Gisela Paola Lazzarino, Oliver Zierau, Jorgelina Varayoud, Milena Durando

{"title":"Glyphosate-based herbicide worsens alterations induced by cafeteria diet on rat uterus","authors":"María Victoria Zanardi, María Paula Gastiazoro, María F. Rossetti, Florencia Doná, Gisela Paola Lazzarino, Oliver Zierau, Jorgelina Varayoud, Milena Durando","doi":"10.1530/joe-24-0071","DOIUrl":"https://doi.org/10.1530/joe-24-0071","url":null,"abstract":"Exposure to glyphosate-based herbicides (GBH) and consumption of cafeteria (CAF) diet, which are widespread in Western society, seem to be associated with endometrial hyperplasia (EH). Here, we aimed to evaluate the effects of a subchronic low dose of a GBH added to CAF diet on the rat uterus. Female Wistar rats were fed from postnatal day (PND)21 until PND240 with chow (Control) or CAF diet. Since PND140, rats also received GBH (2 mg of glyphosate/kg/day) or water through food, yielding four experimental groups: Control, CAF, GBH and CAF+GBH. On PND240, CAF and CAF+GBH animals showed an increased adiposity index. Respect to Control group, no changes on the serum levels of 17β-estradiol and progesterone were found. However, progesterone levels were higher in CAF+GBH group than in CAF and GBH groups. In the uterus, both studied factors alone and in combination induced morphological and molecular changes associated with EH. Furthermore, the addition of GBH provoked an increased thickness of subepithelial stroma in rats fed with CAF diet. As a consequence of GBH exposure, CAF+GBH rats exhibited an increased density of abnormal gland area, considered preneoplastic lesions, as well as a reduced PTEN and p27 expression, both tumor suppressor molecules that inhibit cell proliferation, respect to Control rats. These results indicate that the addition of GBH exacerbates the CAF-effects on uterine lesions and that the PTEN/p27 signaling pathway seems to be involved. Further studies focusing on the interaction between unhealthy diets and environmental chemicals should be encouraged to better understand uterine pathologies.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"1 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586237","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

Urocortin3 contributes to paracrine inhibition of islet alpha cells in mice 尿皮质素3有助于对小鼠胰岛α细胞进行旁分泌抑制

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-04-01 DOI: 10.1530/joe-24-0018

Glyn M. Noguchi, Vincent C. Castillo, Cynthia J. Donaldson, Marcus R. Flisher, Ariana T. Momen, Alan Saghatelian, Mark O. Huising

{"title":"Urocortin3 contributes to paracrine inhibition of islet alpha cells in mice","authors":"Glyn M. Noguchi, Vincent C. Castillo, Cynthia J. Donaldson, Marcus R. Flisher, Ariana T. Momen, Alan Saghatelian, Mark O. Huising","doi":"10.1530/joe-24-0018","DOIUrl":"https://doi.org/10.1530/joe-24-0018","url":null,"abstract":"Pancreatic alpha cell activity and glucagon secretion lowers as glucose levels increase. While part of the decrease is regulated by glucose itself, paracrine signaling by their neighboring beta and delta cells also plays an important role. Somatostatin from delta cells is an important local inhibitor of alpha cells at high glucose. Additionally, Urocortin3 (UCN3) is a hormone that is co-released from beta cells with insulin and acts locally to potentiate somatostatin secretion from delta cells. UCN3 thus inhibits insulin secretion via a negative feedback loop with delta cells, but its role with respect to alpha cells and glucagon secretion is not understood. We hypothesize that the somatostatin-driven glucagon inhibition at high glucose is regulated in part by UCN3 from beta cells. Here, we use a combination of live functional Ca2+ and cAMP imaging as well as direct glucagon secretion measurement, all from alpha cells in intact mouse islets, to determine the contributions of UCN3 to alpha cell behavior. Exogenous UCN3 treatment decreased alpha cell Ca2+ and cAMP levels and inhibited glucagon release. Blocking endogenous UCN3 signaling increased alpha cell Ca2+ by 26.8 ± 7.6%, but this did not result in increased glucagon release at high glucose. Furthermore, constitutive deletion of Ucn3 did not increase Ca2+ activity or glucagon secretion relative to controls. UCN3 is thus capable of inhibiting mouse alpha cells, but, given the subtle effects of endogenous UCN3 signaling on alpha cells, we propose that UCN3-driven somatostatin may serve to regulate local paracrine glucagon levels in the islet instead of inhibiting gross systemic glucagon release.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"78 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586214","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

FSH, bone, belly and brain FSH、骨骼、腹部和大脑

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