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

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

Genome-edited zebrafish model of ABCC8 loss-of-function disease. ABCC8功能丧失疾病的基因组编辑斑马鱼模型。

IF 2.2 4区医学

Islets Pub Date : 2022-12-31 DOI: 10.1080/19382014.2022.2149206

Jennifer M Ikle, Robert C Tryon, Soma S Singareddy, Nathaniel W York, Maria S Remedi, Colin G Nichols

{"title":"Genome-edited zebrafish model of ABCC8 loss-of-function disease.","authors":"Jennifer M Ikle, Robert C Tryon, Soma S Singareddy, Nathaniel W York, Maria S Remedi, Colin G Nichols","doi":"10.1080/19382014.2022.2149206","DOIUrl":"10.1080/19382014.2022.2149206","url":null,"abstract":"ATP-sensitive potassium channel (KATP)gain- (GOF) and loss-of-function (LOF) mutations underlie human neonatal diabetes mellitus (NDM) and hyperinsulinism (HI), respectively. While transgenic mice expressing incomplete KATP LOF do reiterate mild hyperinsulinism, KATP knockout animals do not exhibit persistent hyperinsulinism. We have shown that islet excitability and glucose homeostasis are regulated by identical KATP channels in zebrafish. SUR1 truncation mutation (K499X) was introduced into the abcc8 gene to explore the possibility of using zebrafish for modeling human HI. Patch-clamp analysis confirmed the complete absence of channel activity in β-cells from K499X (SUR1-/-) fish. No difference in random blood glucose was detected in heterozygous SUR1+/- fish nor in homozygous SUR1-/- fish, mimicking findings in SUR1 knockout mice. Mutant fish did, however, demonstrate impaired glucose tolerance, similar to partial LOF mouse models. In paralleling features of mammalian diabetes and hyperinsulinism resulting from equivalent LOF mutations, these gene-edited animals provide valid zebrafish models of KATP -dependent pancreatic diseases.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"14 1","pages":"200-209"},"PeriodicalIF":2.2,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9721409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9115695","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

Impact of biotin supplemented diet on mouse pancreatic islet β-cell mass expansion and glucose induced electrical activity. 添加生物素对小鼠胰岛β细胞增殖和葡萄糖诱导的电活动的影响。

IF 2.2 4区医学

Islets Pub Date : 2022-12-31 DOI: 10.1080/19382014.2022.2091886

Israel Morales-Reyes, Illani Atwater, Marcelino Esparza-Aguilar, E Martha Pérez-Armendariz

{"title":"Impact of biotin supplemented diet on mouse pancreatic islet β-cell mass expansion and glucose induced electrical activity.","authors":"Israel Morales-Reyes, Illani Atwater, Marcelino Esparza-Aguilar, E Martha Pérez-Armendariz","doi":"10.1080/19382014.2022.2091886","DOIUrl":"https://doi.org/10.1080/19382014.2022.2091886","url":null,"abstract":"Biotin supplemented diet (BSD) is known to enhance β-cell replication and insulin secretion in mice. Here, we first describe BSD impact on the islet β-cell membrane potential (Vm) and glucose-induced electrical activity. BALB/c female mice (n ≥ 20) were fed for nine weeks after weaning with a control diet (CD) or a BSD (100X). In both groups, islet area was compared in pancreatic sections incubated with anti-insulin and anti-glucagon antibodies; Vm was recorded in micro dissected islet β-cells during perfusion with saline solutions containing 2.8, 5.0, 7.5-, or 11.0 mM glucose. BSD increased the islet and β-cell area compared with CD. In islet β-cells of the BSD group, a larger ΔVm/Δ[glucose] was found at sub-stimulatory glucose concentrations and the threshold glucose concentration for generation of action potentials (APs) was increased by 1.23 mM. Moreover, at 11.0 mM glucose, a significant decrease was found in AP amplitude, frequency, ascending and descending slopes as well as in the calculated net charge influx and efflux of islet β-cells from BSD compared to the CD group, without changes in slow Vm oscillation parameters. A pharmacological dose of biotin in mice increases islet insulin cell mass, shifts islet β-cell intracellular electrical activity dose response curve toward higher glucose concentrations, very likely by increasing KATP conductance, and decreases voltage gated Ca2+ and K+ conductance at stimulatory glucose concentrations.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"14 1","pages":"149-163"},"PeriodicalIF":2.2,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/91/f2/KISL_14_2091886.PMC9733685.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10382526","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

Impacts of the COVID-19 pandemic on a human research islet program. COVID-19大流行对人类研究岛计划的影响

IF 1.9 4区医学

Islets Pub Date : 2022-12-31 DOI: 10.1080/19382014.2022.2047571

Tina J Dafoe, Theodore Dos Santos, Aliya F Spigelman, James Lyon, Nancy Smith, Austin Bautista, Patrick E MacDonald, Jocelyn E Manning Fox

{"title":"Impacts of the COVID-19 pandemic on a human research islet program.","authors":"Tina J Dafoe, Theodore Dos Santos, Aliya F Spigelman, James Lyon, Nancy Smith, Austin Bautista, Patrick E MacDonald, Jocelyn E Manning Fox","doi":"10.1080/19382014.2022.2047571","DOIUrl":"10.1080/19382014.2022.2047571","url":null,"abstract":"Designated a pandemic in March 2020, the spread of severe acute respiratory syndrome virus 2 (SARS-CoV2), the virus responsible for coronavirus disease 2019 (COVID-19), led to new guidelines and restrictions being implemented for individuals, businesses, and societies in efforts to limit the impacts of COVID-19 on personal health and healthcare systems. Here we report the impacts of the COVID-19 pandemic on pancreas processing and islet isolation/distribution outcomes at the Alberta Diabetes Institute IsletCore, a facility specializing in the processing and distribution of human pancreatic islets for research. While the number of organs processed was significantly reduced, organ quality and the function of cellular outputs were minimally impacted during the pandemic when compared to an equivalent period immediately prior. Despite the maintained quality of isolated islets, feedback from recipient groups was more negative. Our findings suggest this is likely due to disrupted distribution which led to increased transit times to recipient labs, particularly those overseas. Thus, to improve overall outcomes in a climate of limited research islet supply, prioritization of tissue recipients based on likely tissue transit times may be needed.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"14 1","pages":"101-113"},"PeriodicalIF":1.9,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8928860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41757250","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

Dual regulation of miR-375 and CREM genes in pancreatic beta cells 胰腺β细胞中miR-375和CREM基因的双重调控

IF 2.2 4区医学

Islets Pub Date : 2022-04-04 DOI: 10.1080/19382014.2022.2060688

D. Keller, Isis G. Perez

引用次数: 0

Modeling type 2 diabetes in rats by administering tacrolimus 他克莫司对大鼠2型糖尿病的影响

IF 2.2 4区医学

Islets Pub Date : 2022-03-29 DOI: 10.1080/19382014.2022.2051991

J. C. Quintana-Pérez, F. García-Dolores, A. S. Valdez-Guerrero, Diana Alemán-González-Duhart, M. Arellano-Mendoza, S. Rojas Hernández, I. Olivares-Corichi, J. R. García Sánchez, J. T. Trujillo Ferrara, F. Tamay-Cach

{"title":"Modeling type 2 diabetes in rats by administering tacrolimus","authors":"J. C. Quintana-Pérez, F. García-Dolores, A. S. Valdez-Guerrero, Diana Alemán-González-Duhart, M. Arellano-Mendoza, S. Rojas Hernández, I. Olivares-Corichi, J. R. García Sánchez, J. T. Trujillo Ferrara, F. Tamay-Cach","doi":"10.1080/19382014.2022.2051991","DOIUrl":"https://doi.org/10.1080/19382014.2022.2051991","url":null,"abstract":"ABSTRACT The prevalence of diabetes is rapidly increasing. The current number of diagnosed cases is ~422 million, expected to reach ~640 million by 2040. Type 2 diabetes, which constitutes ~95% of the cases, is characterized by insulin resistance and a progressive loss of β-cell function. Despite intense research efforts, no treatments are yet able to cure the disease or halt its progression. Since all existing animal models of type 2 diabetes have serious drawbacks, one is needed that represents the complete pathogenesis, is low cost and non-obese, and can be developed relatively quickly. The aim of this study was to evaluate a low-cost, non-obese model of type 2 diabetes engendered by administering a daily high dose of tacrolimus (an immunosuppressant) to Wistar rats for 4 weeks. The biochemical and antioxidant markers were measured at basal and after the 4-week tacrolimus treatment. At week 4, the values of these parameters closely resembled those observed in human type 2 diabetes, including fasting blood glucose at 141.5 mg/dL, blood glucose greater than 200 mg/dL at 120 min of the glucose tolerance test, blood glucose at varied levels in the insulin tolerance test, and elevated levels of cholesterol and triglyceride. The tacrolimus treatment produced hypoinsulinemia and sustained hyperglycemia, probably explained by the alteration found in pancreatic β-cell function and morphology. This model should certainly be instrumental for evaluating possible type 2 diabetes treatments, and for designing new immunosuppressants that do not cause pancreatic damage, type 2 diabetes, or new-onset diabetes after transplantation (NODAT).","PeriodicalId":14671,"journal":{"name":"Islets","volume":"14 1","pages":"114 - 127"},"PeriodicalIF":2.2,"publicationDate":"2022-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45875558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 3

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