IF 1.9 4区医学

Islets Pub Date : 2024-12-31 Epub Date: 2024-08-18 DOI: 10.1080/19382014.2024.2392343

Bssam Aljani, Annett Lindner, Marc Weigelt, Min Zhao, Virag Sharma, Ezio Bonifacio, Peter Jones, Anne Eugster

{"title":"Small RNA-Seq and real time rt-qPCR reveal islet miRNA released under stress conditions.","authors":"Bssam Aljani, Annett Lindner, Marc Weigelt, Min Zhao, Virag Sharma, Ezio Bonifacio, Peter Jones, Anne Eugster","doi":"10.1080/19382014.2024.2392343","DOIUrl":"10.1080/19382014.2024.2392343","url":null,"abstract":"Replacement of beta cells through transplantation is a potential therapeutic approach for individuals with pancreas removal or poorly controllable type 1 diabetes. However, stress and death of beta cells pose significant challenges. Circulating miRNA has emerged as potential biomarkers reflecting early beta cell stress and death, allowing for timely intervention. The aim of this study was to identify miRNAs as potential biomarkers for beta cell health. Literature review combined with small RNA sequencing was employed to select islet-enriched miRNA. The release of those miRNA was assessed by RT-qPCR in vivo, using a streptozotocin induced diabetes mouse model and in vitro, through mouse and human islets exposed to varying degrees of hypoxic and cytokine stressors. Utilizing the streptozotocin induced model, we identified 18 miRNAs out of 39 candidate islet-enriched miRNA to be released upon islet stress in vivo. In vitro analysis of culture supernatants from cytokine and/or hypoxia stressed islets identified the release of 45 miRNAs from mouse and 8 miRNAs from human islets. Investigation into the biological pathways targeted by the cytokine- and/or hypoxia-induced miRNA suggested the involvement of MAPK and PI3K-Akt signaling pathways in both mouse and human islets. We have identified miRNAs associated with beta cell health and stress. The findings allowed us to propose a panel of 47 islet-related human miRNA that is potentially valuable for application in clinical contexts of beta cell transplantation and presymptomatic early-stage type 1 diabetes.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"16 1","pages":"2392343"},"PeriodicalIF":1.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Changes in immunofluorescence staining during islet regeneration in a cystic fibrosis-related diabetes (CFRD) ferret model. 囊性纤维化相关性糖尿病（CFRD）雪貂模型胰岛再生过程中免疫荧光染色的变化

IF 1.9 4区医学

Islets Pub Date : 2024-12-31 Epub Date: 2024-12-06 DOI: 10.1080/19382014.2024.2436696

Sawash M Mohammed, Robert N Bone, Jacqueline Del Carmen Aquino, Raghavendra G Mirmira, Carmella Evans-Molina, Heba M Ismail

{"title":"Changes in immunofluorescence staining during islet regeneration in a cystic fibrosis-related diabetes (CFRD) ferret model.","authors":"Sawash M Mohammed, Robert N Bone, Jacqueline Del Carmen Aquino, Raghavendra G Mirmira, Carmella Evans-Molina, Heba M Ismail","doi":"10.1080/19382014.2024.2436696","DOIUrl":"10.1080/19382014.2024.2436696","url":null,"abstract":"Background: Knockout (KO) ferrets with the cystic fibrosis transmembrane conductance regulator (CFTR) exhibit distinct phases of dysglycemia and pancreatic remodeling prior to cystic fibrosis-related diabetes (CFRD) development. Following normoglycemia during the first month of life (Phase l), hyperglycemia occurs during the subsequent 2 months (Phase Il) with decreased islet mass, followed by a period of near normoglycemia (Phase Ill) in which the islets regenerate. We aimed to characterize islet hormone expression patterns across these Phases.Methods: Immunofluorescence staining per islet area was performed to characterize islet hormone expression patterns in age matched CFTR KO and wild type (WT) ferrets, focusing on the first three phases.Results: In Phase I, insulin staining intensity was higher in CF (p < 0.01) than WT but decreased in Phase III (p < 0.0001). Glucagon was lower in CF during Phases I and increased in Phase III, while proinsulin decreased (p < 0.0001) Phases II and III. CF sections showed lower proinsulin-to-insulin ratio in Phase I (p < 0.01) and in Phase III (p < 0.05) compared to WT. Conversely, glucagon-to-insulin ratio was lower in CF in Phase I (p < 0.0001) but increased in Phase III (p < 0.0001). Mender's coefficient overlap showed higher overlap of insulin over proinsulin in CF sections in Phase II (p < 0.001) and Phase III (p < 0.0001) compared to WT. Mender's coefficient rate was higher in CF sections during Phase II (p < 0.001).Conclusion: CF ferret islets revealed significant immunofluorescent staining changes compared to WT during various phases of disease, providing insights into CRFD pathophysiology.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"16 1","pages":"2436696"},"PeriodicalIF":1.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

β cell acetate production and release are negligible β 细胞醋酸盐的产生和释放可以忽略不计

IF 2.2 4区医学

Islets Pub Date : 2024-04-12 DOI: 10.1080/19382014.2024.2339558

Kai Xu, Chioma Nnyamah, Nupur Pandya, Nadia Sweis, Irene Corona-Avila, Medha Priyadarshini, Barton Wicksteed, Brian T. Layden

引用次数: 0

IsletSwipe, a mobile platform for expert opinion exchange on islet graft images. 胰岛移植物影像专家意见交流移动平台IsletSwipe。

IF 1.9 4区医学

Islets Pub Date : 2023-12-31 DOI: 10.1080/19382014.2023.2189873

David Habart, Adam Koza, Ivan Leontovyc, Lucie Kosinova, Zuzana Berkova, Jan Kriz, Klara Zacharovova, Bas Brinkhof, Dirk-Jan Cornelissen, Nicholas Magrane, Katerina Bittenglova, Martin Capek, Jan Valecka, Alena Habartova, František Saudek

{"title":"IsletSwipe, a mobile platform for expert opinion exchange on islet graft images.","authors":"David Habart, Adam Koza, Ivan Leontovyc, Lucie Kosinova, Zuzana Berkova, Jan Kriz, Klara Zacharovova, Bas Brinkhof, Dirk-Jan Cornelissen, Nicholas Magrane, Katerina Bittenglova, Martin Capek, Jan Valecka, Alena Habartova, František Saudek","doi":"10.1080/19382014.2023.2189873","DOIUrl":"10.1080/19382014.2023.2189873","url":null,"abstract":"We previously developed a deep learning-based web service (IsletNet) for an automated counting of isolated pancreatic islets. The neural network training is limited by the absent consensus on the ground truth annotations. Here, we present a platform (IsletSwipe) for an exchange of graphical opinions among experts to facilitate the consensus formation. The platform consists of a web interface and a mobile application. In a small pilot study, we demonstrate the functionalities and the use case scenarios of the platform. Nine experts from three centers validated the drawing tools, tested precision and consistency of the expert contour drawing, and evaluated user experience. Eight experts from two centers proceeded to evaluate additional images to demonstrate the following two use case scenarios. The Validation scenario involves an automated selection of images and islets for the expert scrutiny. It is scalable (more experts, images, and islets may readily be added) and can be applied to independent validation of islet contours from various sources. The Inquiry scenario serves the ground truth generating expert in seeking assistance from peers to achieve consensus on challenging cases during the preparation for IsletNet training. This scenario is limited to a small number of manually selected images and islets. The experts gained an opportunity to influence IsletNet training and to compare other experts' opinions with their own. The ground truth-generating expert obtained feedback for future IsletNet training. IsletSwipe is a suitable tool for the consensus finding. Experts from additional centers are welcome to participate.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"15 1","pages":"2189873"},"PeriodicalIF":1.9,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9819762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Beta cell primary cilia mediate somatostatin responsiveness via SSTR3. 细胞原代纤毛通过SSTR3介导生长抑素反应。

IF 2.2 4区医学

Islets Pub Date : 2023-12-31 DOI: 10.1080/19382014.2023.2252855

Samantha E Adamson, Zipeng A Li, Jing W Hughes

{"title":"Beta cell primary cilia mediate somatostatin responsiveness via SSTR3.","authors":"Samantha E Adamson, Zipeng A Li, Jing W Hughes","doi":"10.1080/19382014.2023.2252855","DOIUrl":"10.1080/19382014.2023.2252855","url":null,"abstract":"Somatostatin is a paracrine modulator of insulin secretion and beta cell function with pleotropic effects on glucose homeostasis. The mechanism of somatostatin-mediated communication between delta and beta cells is not well-understood, which we address in this study via the ciliary somatostatin receptor 3 (SSTR3). Primary cilia are membrane organelles that act as signaling hubs in islets by virtue of their subcellular location and enrichment in signaling proteins such as G-protein coupled receptors (GPCRs). We show that SSTR3, a ciliary GPCR, mediates somatostatin suppression of insulin secretion in mouse islets. Quantitative analysis of calcium flux using a mouse model of genetically encoded beta cell-specific GCaMP6f calcium reporter shows that somatostatin signaling alters beta cell calcium flux after physiologic glucose stimulation, an effect that depends on endogenous SSTR3 expression and the presence of intact primary cilia on beta cells. Comparative in vitro studies using SSTR isoform antagonists demonstrate a role for SSTR3 in mediating somatostatin regulation of insulin secretion in mouse islets. Our findings support a model in which ciliary SSTR3 mediates a distinct pathway of delta-to-beta cell regulatory crosstalk and may serve as a target for paracrine modulation.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"15 1","pages":"2252855"},"PeriodicalIF":2.2,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10178767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamic regulation of pancreatic β cell function and gene expression by the SND1 coregulator in vitro. SND1协同调节器对胰腺β细胞功能和基因表达的动态调节。

IF 2.2 4区医学

Islets Pub Date : 2023-12-31 Epub Date: 2023-10-15 DOI: 10.1080/19382014.2023.2267725

Sukrati Kanojia, Rebecca K Davidson, Jason M Conley, Jerry Xu, Meredith Osmulski, Emily K Sims, Hongxia Ren, Jason M Spaeth

{"title":"Dynamic regulation of pancreatic β cell function and gene expression by the SND1 coregulator in vitro.","authors":"Sukrati Kanojia, Rebecca K Davidson, Jason M Conley, Jerry Xu, Meredith Osmulski, Emily K Sims, Hongxia Ren, Jason M Spaeth","doi":"10.1080/19382014.2023.2267725","DOIUrl":"10.1080/19382014.2023.2267725","url":null,"abstract":"The pancreatic β cell synthesizes, packages, and secretes insulin in response to glucose-stimulation to maintain blood glucose homeostasis. Under diabetic conditions, a subset of β cells fail and lose expression of key transcription factors (TFs) required for insulin secretion. Among these TFs is Pancreatic and duodenal homeobox 1 (PDX1), which recruits a unique subset of transcriptional coregulators to modulate its activity. Here we describe a novel interacting partner of PDX1, the Staphylococcal Nuclease and Tudor domain-containing protein (SND1), which has been shown to facilitate protein-protein interactions and transcriptional control through diverse mechanisms in a variety of tissues. PDX1:SND1 interactions were confirmed in rodent β cell lines, mouse islets, and human islets. Utilizing CRISPR-Cas9 gene editing technology, we deleted Snd1 from the mouse β cell lines, which revealed numerous differentially expressed genes linked to insulin secretion and cell proliferation, including limited expression of Glp1r. We observed Snd1 deficient β cell lines had reduced cell expansion rates, GLP1R protein levels, and limited cAMP accumulation under stimulatory conditions, and further show that acute ablation of Snd1 impaired insulin secretion in rodent and human β cell lines. Lastly, we discovered that PDX1:SND1 interactions were profoundly reduced in human β cells from donors with type 2 diabetes (T2D). These observations suggest the PDX1:SND1 complex formation is critical for controlling a subset of genes important for β cell function and is targeted in diabetes pathogenesis.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"15 1","pages":"2267725"},"PeriodicalIF":2.2,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10578191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41235236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EP3 signaling is decoupled from the regulation of glucose-stimulated insulin secretion in β-cells compensating for obesity and insulin resistance. EP3信号与补偿肥胖和胰岛素抵抗的β细胞中葡萄糖刺激的胰岛素分泌的调节脱钩。

IF 1.9 4区医学

Islets Pub Date : 2023-12-31 DOI: 10.1080/19382014.2023.2223327

Michael D Schaid, Jeffrey M Harrington, Grant M Kelly, Sophia M Sdao, Matthew J Merrins, Michelle E Kimple

{"title":"EP3 signaling is decoupled from the regulation of glucose-stimulated insulin secretion in β-cells compensating for obesity and insulin resistance.","authors":"Michael D Schaid, Jeffrey M Harrington, Grant M Kelly, Sophia M Sdao, Matthew J Merrins, Michelle E Kimple","doi":"10.1080/19382014.2023.2223327","DOIUrl":"10.1080/19382014.2023.2223327","url":null,"abstract":"Of the β-cell signaling pathways altered by obesity and insulin resistance, some are adaptive while others contribute to β-cell failure. Two critical second messengers are Ca2+ and cAMP, which control the timing and amplitude of insulin secretion. Previous work has shown the importance of the cAMP-inhibitory Prostaglandin EP3 receptor (EP3) in mediating the β-cell dysfunction of type 2 diabetes (T2D). Here, we used three groups of C57BL/6J mice as a model of the progression from metabolic health to T2D: wildtype, normoglycemic LeptinOb (NGOB), and hyperglycemic LeptinOb (HGOB). Robust increases in β-cell cAMP and insulin secretion were observed in NGOB islets as compared to wildtype controls; an effect lost in HGOB islets, which exhibited reduced β-cell cAMP and insulin secretion despite increased glucose-dependent Ca2+ influx. An EP3 antagonist had no effect on β-cell cAMP or Ca2+ oscillations, demonstrating agonist-independent EP3 signaling. Finally, using sulprostone to hyperactivate EP3 signaling, we found EP3-dependent suppression of β-cell cAMP and Ca2+ duty cycle effectively reduces insulin secretion in HGOB islets, while having no impact insulin secretion on NGOB islets, despite similar and robust effects on cAMP levels and Ca2+ duty cycle. Finally, increased cAMP levels in NGOB islets are consistent with increased recruitment of the small G protein, Rap1GAP, to the plasma membrane, sequestering the EP3 effector, Gɑz, from inhibition of adenylyl cyclase. Taken together, these results suggest that rewiring of EP3 receptor-dependent cAMP signaling contributes to the progressive changes in β cell function observed in the LeptinOb model of diabetes.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"15 1","pages":"2223327"},"PeriodicalIF":1.9,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10332234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9796206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A primer on modelling pancreatic islets: from models of coupled β-cells to multicellular islet models. 胰岛模型入门:从偶联β细胞模型到多细胞胰岛模型。

IF 1.9 4区医学

Islets Pub Date : 2023-12-31 DOI: 10.1080/19382014.2023.2231609

Gerardo J Félix-Martínez, J Rafael Godínez-Fernández

引用次数: 0

The causal relationship between bacterial pneumonia and diabetes: a two-sample mendelian randomization study 细菌性肺炎与糖尿病之间的因果关系：双样本泯灭随机研究

IF 2.2 4区医学

Islets Pub Date : 2023-12-14 DOI: 10.1080/19382014.2023.2291885

Songying Pan, Zhongqi Zhang, Weiyi Pang

引用次数: 0

Species-dependent impact of immunosuppressive squalene-gusperimus nanoparticles and adipose-derived stem cells on isolated human and rat pancreatic islets. 免疫抑制角鲨烯-谷氨酸纳米颗粒和脂肪来源的干细胞对分离的人和大鼠胰岛的物种依赖性影响。

IF 2.2 4区医学

Islets Pub Date : 2022-12-31 DOI: 10.1080/19382014.2022.2100191

Carlos E Navarro Chica, Tian Qin, Erika Pinheiro-Machado, Bart J de Haan, M M Faas, Alexandra M Smink, Ligia Sierra, Betty L López, Paul de Vos

{"title":"Species-dependent impact of immunosuppressive squalene-gusperimus nanoparticles and adipose-derived stem cells on isolated human and rat pancreatic islets.","authors":"Carlos E Navarro Chica, Tian Qin, Erika Pinheiro-Machado, Bart J de Haan, M M Faas, Alexandra M Smink, Ligia Sierra, Betty L López, Paul de Vos","doi":"10.1080/19382014.2022.2100191","DOIUrl":"https://doi.org/10.1080/19382014.2022.2100191","url":null,"abstract":"Transplantation of pancreatic islets is a promising approach to controlling glucose levels in type 1 diabetes mellitus (T1DM), but islet survival is still limited. To overcome this, islet co-culture with mesenchymal stromal cells (MSCs) together with safe immunosuppressive agents like squalene-gusperimus nanoparticles (Sq-GusNPs) may be applied. This could support islet survival and engraftment. Here, we studied how Sq-GusNPs and adipose-derived stem cells (ASCs) influence islets response under pro-inflammatory conditions. Through qRT-PCR, we studied the expression of specific genes at 24 hours in human and rat islets and ASCs in co-culture under indirect contact with or without treatment with Sq-GusNPs. We characterized how the response of islets and ASCs starts at molecular level before impaired viability or function is observed and how this response differs between species. Human islets and ASCs responses showed to be principally influenced by NF-κB activation, whereas rat islet and ASCs responses showed to be principally mediated by nitrosative stress. Rat islets showed tolerance to inflammatory conditions due to IL-1Ra secretion which was also observed in rat ASCs. Human islets induced the expression of cytokines and chemokines with pro-angiogenic, tissue repair, and anti-apoptotic properties in human ASCs under basal conditions. This expression was not inhibited by Sq-GusNPs. Our results showed a clear difference in the response elicited by human and rat islets and ASCs in front of an inflammatory stimulus and Sq-GusNPs. Our data support the use of ASCs and Sq-GusNP to facilitate engraftment of islets for T1DM treatment.","PeriodicalId":14671,"journal":{"name":"Islets","volume":" ","pages":"164-183"},"PeriodicalIF":2.2,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40507811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

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