IF 1.9 4区医学

Islets Pub Date : 2024-12-31 Epub Date: 2024-06-04 DOI: 10.1080/19382014.2024.2361996

Kyle A van Allen, Noa Gang, Myriam P Hoyeck, Ineli Perera, Dahai Zhang, Ella Atlas, Francis C Lynn, Jennifer E Bruin

{"title":"Characterizing the effects of Dechlorane Plus on β-cells: a comparative study across models and species.","authors":"Kyle A van Allen, Noa Gang, Myriam P Hoyeck, Ineli Perera, Dahai Zhang, Ella Atlas, Francis C Lynn, Jennifer E Bruin","doi":"10.1080/19382014.2024.2361996","DOIUrl":"10.1080/19382014.2024.2361996","url":null,"abstract":"Epidemiological studies consistently link environmental toxicant exposure with increased Type 2 diabetes risk. Our study investigated the diabetogenic effects of a widely used flame retardant, Dechlorane Plus (DP), on pancreatic β-cells using rodent and human model systems. We first examined pancreas tissues from male mice exposed daily to oral gavage of either vehicle (corn oil) or DP (10, 100, or 1000 μg/kg per day) and fed chow or high fat diet for 28-days in vivo. DP exposure did not affect islet size or endocrine cell composition in either diet group. Next, we assessed the effect of 48-hour exposure to vehicle (DMSO) or DP (1, 10, or 100 nM) in vitro using immortalized rat β-cells (INS-1 832/3), primary mouse and human islets, and human stem-cell derived islet-like cells (SC-islets). In INS-1 832/3 cells, DP did not impact glucose-stimulated insulin secretion (GSIS) but significantly decreased intracellular insulin content. DP had no effect on GSIS in mouse islets or SC-islets but had variable effects on GSIS in human islets depending on the donor. DP alone did not affect insulin content in mouse islets, human islets, or SC-islets, but mouse islets co-exposed to DP and glucolipotoxic (GLT) stress conditions (28.7 mM glucose + 0.5 mM palmitate) had reduced insulin content compared to control conditions. Co-exposure of mouse islets to DP + GLT amplified the upregulation of Slc30a8 compared to GLT alone. Our study highlights the importance and challenges of using different in vitro models for studying chemical toxicity.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"16 1","pages":"2361996"},"PeriodicalIF":1.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11152096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247540","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

Neuregulin 4 attenuates pancreatic β-cell apoptosis induced by lipotoxicity via activating mTOR-mediated autophagy. Neuregulin 4通过激活mTOR介导的自噬减轻脂肪毒性诱导的胰腺β细胞凋亡

IF 1.9 4区医学

Islets Pub Date : 2024-12-31 Epub Date: 2024-11-14 DOI: 10.1080/19382014.2024.2429854

Biao Zhu, Lei Sun, Junyao Tong, Yan Ding, Yanbo Shan, Mingjuan He, Xiaoyu Tian, Wen Mei, Lisheng Zhao, Ying Wang

{"title":"Neuregulin 4 attenuates pancreatic β-cell apoptosis induced by lipotoxicity via activating mTOR-mediated autophagy.","authors":"Biao Zhu, Lei Sun, Junyao Tong, Yan Ding, Yanbo Shan, Mingjuan He, Xiaoyu Tian, Wen Mei, Lisheng Zhao, Ying Wang","doi":"10.1080/19382014.2024.2429854","DOIUrl":"10.1080/19382014.2024.2429854","url":null,"abstract":"Neuregulin 4 (Nrg4) is a brown fat-enriched endocrine factor that ameliorates lipid metabolism disorders. Autophagy is critical for pancreatic β-cell to counteract lipotoxicity-induced apoptosis. This study aimed at exploring whether Nrg4 attenuates lipotoxicity-induced β-cell apoptosis by regulating autophagy. The mouse pancreatic β-cell line MIN6 was cultured in palmitic acid (PA) with or without Nrg4 administration. Apoptosis rate, together with anti-apoptotic and pro-apoptotic protein levels, was investigated. Autophagic flux and autophagy-related protein levels along with related signaling pathways that regulate autophagy were also evaluated. Results showed that Nrg4 decreased PA-induced MIN6 apoptosis, enhanced anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) expression and reduced pro-apoptotic proteins Bcl-2-associated X protein (Bax) and cleaved-caspase 3 expressions. Autophagy levels in MIN6 also decreased with PA treatment and Nrg4 administration reactivated autophagy. Further, Nrg4 administration activated autophagy via the mammalian target of rapamycin (mTOR) signaling pathway. In addition, when the mTOR pathway was stimulated or autophagy was suppressed, the beneficial effects of Nrg4 administration on MIN6 apoptosis were diminished. These results imply that Nrg4 administration attenuates MIN6 apoptosis by promoting mTOR-dependent autophagy and thus may lead to a new therapeutic method for type 2 diabetes mellitus (T2DM).","PeriodicalId":14671,"journal":{"name":"Islets","volume":"16 1","pages":"2429854"},"PeriodicalIF":1.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620703","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

Serum from pregnant donors induces human beta cell proliferation. 怀孕供体的血清可诱导人类 beta 细胞增殖。

IF 1.9 4区医学

Islets Pub Date : 2024-12-31 Epub Date: 2024-03-27 DOI: 10.1080/19382014.2024.2334044

Kendra R Sylvester-Armstrong, Callie F Reeder, Andrece Powell, Matthew W Becker, D Walker Hagan, Jing Chen, Clayton E Mathews, Clive H Wasserfall, Mark A Atkinson, Robert Egerman, Edward A Phelps

{"title":"Serum from pregnant donors induces human beta cell proliferation.","authors":"Kendra R Sylvester-Armstrong, Callie F Reeder, Andrece Powell, Matthew W Becker, D Walker Hagan, Jing Chen, Clayton E Mathews, Clive H Wasserfall, Mark A Atkinson, Robert Egerman, Edward A Phelps","doi":"10.1080/19382014.2024.2334044","DOIUrl":"10.1080/19382014.2024.2334044","url":null,"abstract":"Pancreatic beta cells are among the slowest replicating cells in the human body and have not been observed to increase in number except during the fetal and neonatal period, in cases of obesity, during puberty, as well as during pregnancy. Pregnancy is associated with increased beta cell mass to meet heightened insulin demands. This phenomenon raises the intriguing possibility that factors present in the serum of pregnant individuals may stimulate beta cell proliferation and offer insights into expansion of the beta cell mass for treatment and prevention of diabetes. The primary objective of this study was to test the hypothesis that serum from pregnant donors contains bioactive factors capable of inducing human beta cell proliferation. An immortalized human beta cell line with protracted replication (EndoC-βH1) was cultured in media supplemented with serum from pregnant and non-pregnant female and male donors and assessed for differences in proliferation. This experiment was followed by assessment of proliferation of primary human beta cells. Sera from five out of six pregnant donors induced a significant increase in the proliferation rate of EndoC-βH1 cells. Pooled serum from the cohort of pregnant donors also increased the rate of proliferation in primary human beta cells. This study demonstrates that serum from pregnant donors stimulates human beta cell proliferation. These findings suggest the existence of pregnancy-associated factors that can offer novel avenues for beta cell regeneration and diabetes prevention strategies. Further research is warranted to elucidate the specific factors responsible for this effect.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"16 1","pages":"2334044"},"PeriodicalIF":1.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10978022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293513","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

Human research islet cell culture outcomes at the Alberta Diabetes Institute IsletCore. 阿尔伯塔糖尿病研究所胰岛核心的人类研究胰岛细胞培养成果。

IF 1.9 4区医学

Islets Pub Date : 2024-12-31 Epub Date: 2024-08-04 DOI: 10.1080/19382014.2024.2385510

James G Lyon, Alice Lj Carr, Nancy P Smith, Braulio Marfil-Garza, Aliya F Spigelman, Austin Bautista, Doug O'Gorman, Tatsuya Kin, Am James Shapiro, Peter A Senior, Patrick E MacDonald

{"title":"Human research islet cell culture outcomes at the Alberta Diabetes Institute IsletCore.","authors":"James G Lyon, Alice Lj Carr, Nancy P Smith, Braulio Marfil-Garza, Aliya F Spigelman, Austin Bautista, Doug O'Gorman, Tatsuya Kin, Am James Shapiro, Peter A Senior, Patrick E MacDonald","doi":"10.1080/19382014.2024.2385510","DOIUrl":"10.1080/19382014.2024.2385510","url":null,"abstract":"Human islets from deceased organ donors have made important contributions to our understanding of pancreatic endocrine function and continue to be an important resource for research studies aimed at understanding, treating, and preventing diabetes. Understanding the impacts of isolation and culture upon the yield of human islets for research is important for planning research studies and islet distribution to distant laboratories. Here, we examine islet isolation and cell culture outcomes at the Alberta Diabetes Institute (ADI) IsletCore (n = 197). Research-focused isolations typically have a lower yield of islet equivalents (IEQ), with a median of 252,876 IEQ, but a higher purity (median 85%) than clinically focused isolations before culture. The median recovery of IEQs after culture was 75%, suggesting some loss. This was associated with a shift toward smaller islet particles, indicating possible islet fragmentation, and occurred within 24 h with no further loss after longer periods of culture (up to 136 h). No overall change in stimulation index as a measure of islet function was seen with culture time. These findings were replicated in a representative cohort of clinical islet preparations from the Clinical Islet Transplant Program at the University of Alberta. Thus, loss of islets occurs within 24 h of isolation, and there is no further impact of extended culture prior to islet distribution for research.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"16 1","pages":"2385510"},"PeriodicalIF":1.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889263","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

Small RNA-Seq and real time rt-qPCR reveal islet miRNA released under stress conditions. 小 RNA-Seq 和实时 rt-qPCR 揭示了应激条件下释放的胰岛 miRNA。

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

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