IF 2.2 4区医学

Islets Pub Date : 2021-09-03 Epub Date: 2021-09-09 DOI: 10.1080/19382014.2021.1963188

James R Wright

{"title":"Frederick Banting's actual great idea: The role of fetal bovine islets in the discovery of insulin.","authors":"James R Wright","doi":"10.1080/19382014.2021.1963188","DOIUrl":"10.1080/19382014.2021.1963188","url":null,"abstract":"Background: Frederick Banting approached Toronto physiology professor JJR Macleod with a way to prevent pancreatic trypsin from destroying the pancreas' internal secretion. Banting proposed to induce exocrine atrophy by ligating canine pancreatic ducts and to use extracts of islet-rich residua to treat pancreatectomized dogs. His next plan was to make extracts from fetal pancreas, which he had read was islet-rich and lacked exocrine tissue capable of making trypsin; this work has not been historically evaluated.Methods: Banting's fetal calf pancreas story is told using primary and secondary historical sources and then critically examined using both historical and recent data on species phylogeny, islet ontogeny, fetal/neonatal islet culture/transplantation, etc. Results/Discussion: Only ruminants develop dual islets populations sequentially; fetal calf pancreata, at the gestational ages Banting used, possess numerous insulin-rich giant peri-lobular islets, which credibly explain the potency of his fetal calf insulin extract. Use of non-ruminant fetal pancreata would have failed.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"13 5-6","pages":"121-133"},"PeriodicalIF":2.2,"publicationDate":"2021-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/6c/KISL_13_1963188.PMC8528409.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39398410","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: 5

The Potential of Pancreatic Organoids for Diabetes Research and Therapy. 胰腺器官组织用于糖尿病研究和治疗的潜力

IF 1.9 4区医学

Islets Pub Date : 2021-09-03 Epub Date: 2021-09-15 DOI: 10.1080/19382014.2021.1941555

Katerina Bittenglova, David Habart, Frantisek Saudek, Tomas Koblas

{"title":"The Potential of Pancreatic Organoids for Diabetes Research and Therapy.","authors":"Katerina Bittenglova, David Habart, Frantisek Saudek, Tomas Koblas","doi":"10.1080/19382014.2021.1941555","DOIUrl":"10.1080/19382014.2021.1941555","url":null,"abstract":"The success of clinical transplantation of pancreas or isolated pancreatic islets supports the concept of cell-based cure for diabetes. One limitation is the shortage of cadaver human pancreata. The demand-supply gap could potentially be bridged by harnessing the self-renewal capacity of stem cells. Pluripotent stem cells and adult pancreatic stem cells have been explored as possible cell sources. Recently, a system for long-term culture of proposed adult pancreatic stem cells in a form of organoids was developed. Generated organoids partially mimic the architecture and cell-type composition of pancreatic tissue. Here, we review the attempts over the past decade, to utilize the organoid cell culture principles in order to identify, expand, and differentiate the adult pancreatic stem cells from different compartments of mouse and human pancreata. The development of the culture conditions, effects of specific growth factors and small molecules is discussed. The potential utility of the adult pancreatic stem cells is considered in the context of other cell sources.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"13 5-6","pages":"85-105"},"PeriodicalIF":1.9,"publicationDate":"2021-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528407/pdf/KISL_13_1941555.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39417048","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

Hnf1b-CreER causes efficient recombination of a Rosa26-RFP reporter in duct and islet δ cells. Hnf1b-CreER在导管和胰岛δ细胞中引起Rosa26-RFP报告基因的有效重组。

IF 2.2 4区医学

Islets Pub Date : 2021-09-03 Epub Date: 2021-07-20 DOI: 10.1080/19382014.2021.1955088

Meritxell Rovira, Miguel Angel Maestro, Vanessa Grau, Jorge Ferrer

{"title":"Hnf1b-CreER causes efficient recombination of a Rosa26-RFP reporter in duct and islet δ cells.","authors":"Meritxell Rovira, Miguel Angel Maestro, Vanessa Grau, Jorge Ferrer","doi":"10.1080/19382014.2021.1955088","DOIUrl":"https://doi.org/10.1080/19382014.2021.1955088","url":null,"abstract":"The Hnf1b-CreERT2 BAC transgenic (Tg(Hnf1b-cre/ERT2)1Jfer) has been used extensively to trace the progeny of pancreatic ducts in developmental, regeneration, or cancer models. Hnf1b-CreERT2 transgenics have been used to show that the cells that form the embryonic pancreas duct-like plexus are bipotent duct-endocrine progenitors, whereas adult mouse duct cells are not a common source of β cells in various regenerative settings. The interpretation of such genetic lineage tracing studies is critically dependent on a correct understanding of the cell type specificity of recombinase activity with each reporter system. We have reexamined the performance of Hnf1b-CreERT2 with a Rosa26-RFP reporter transgene. This showed inducible recombination of up to 96% adult duct cells, a much higher efficiency than previously used reporter transgenes. Despite this high duct-cell excision, recombination in α and β cells remained very low, similar to previously used reporters. However, nearly half of somatostatin-expressing δ cells showed reporter activation, which was due to Cre expression in δ cells rather than to duct to δ cell conversions. The high recombination efficiency in duct cells indicates that the Hnf1b-CreERT2 model can be useful for both ductal fate mapping and genetic inactivation studies. The recombination in δ cells does not modify the interpretation of studies that failed to show duct conversions to other cell types, but needs to be considered if this model is used in studies that aim to modify the plasticity of pancreatic duct cells.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"13 5-6","pages":"134-139"},"PeriodicalIF":2.2,"publicationDate":"2021-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2021.1955088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39202054","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: 3

Expression of SARS-CoV-2 receptor "ACE2" in human pancreatic β cells: to be or not to be! SARS-CoV-2受体“ACE2”在人胰腺β细胞中的表达:生存还是毁灭!

IF 2.2 4区医学

Islets Pub Date : 2021-09-03 Epub Date: 2021-07-24 DOI: 10.1080/19382014.2021.1954458

Waseem El-Huneidi, Mawieh Hamad, Jalal Taneera

引用次数: 12

Not so sweet and simple: impacts of SARS-CoV-2 on the β cell. 不那么甜蜜和简单：SARS-CoV-2 对 β 细胞的影响。

IF 2.2 4区医学

Islets Pub Date : 2021-07-04 Epub Date: 2021-05-10 DOI: 10.1080/19382014.2021.1909970

Sarah Ibrahim, Gabriela S F Monaco, Emily K Sims

{"title":"Not so sweet and simple: impacts of SARS-CoV-2 on the β cell.","authors":"Sarah Ibrahim, Gabriela S F Monaco, Emily K Sims","doi":"10.1080/19382014.2021.1909970","DOIUrl":"10.1080/19382014.2021.1909970","url":null,"abstract":"The link between COVID-19 infection and diabetes has been explored in several studies since the start of the pandemic, with associations between comorbid diabetes and poorer prognosis in patients infected with the virus and reports of diabetic ketoacidosis occurring with COVID-19 infection. As such, significant interest has been generated surrounding mechanisms by which the virus may exert effects on the pancreatic β cells. In this review, we consider possible routes by which SARS-CoV-2 may impact β cells. Specifically, we outline data that either support or argue against the idea of direct infection and injury of β cells by SARS-CoV-2. We also discuss β cell damage due to a \"bystander\" effect in which infection with the virus leads to damage to surrounding tissues that are essential for β cell survival and function, such as the pancreatic microvasculature and exocrine tissue. Studies elucidating the provocation of a cytokine storm following COVID-19 infection and potential impacts of systemic inflammation and increases in insulin resistance on β cells are also reviewed. Finally, we summarize the existing clinical data surrounding diabetes incidence since the start of the COVID-19 pandemic.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"13 3-4","pages":"66-79"},"PeriodicalIF":2.2,"publicationDate":"2021-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fe/2e/KISL_13_1909970.PMC8281101.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38897847","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 functional genomic approach to identify reference genes for human pancreatic beta cell real-time quantitative RT-PCR analysis. 人类胰腺β细胞实时定量RT-PCR分析的功能基因组学方法鉴定内参基因。

IF 1.7 4区医学

Islets Pub Date : 2021-07-04 Epub Date: 2021-07-09 DOI: 10.1080/19382014.2021.1948282

Maria Inês Alvelos, Florian Szymczak, Ângela Castela, Sandra Marín-Cañas, Bianca Marmontel de Souza, Ioannis Gkantounas, Maikel Colli, Federica Fantuzzi, Cristina Cosentino, Mariana Igoillo-Esteve, Lorella Marselli, Piero Marchetti, Miriam Cnop, Décio L Eizirik

{"title":"A functional genomic approach to identify reference genes for human pancreatic beta cell real-time quantitative RT-PCR analysis.","authors":"Maria Inês Alvelos, Florian Szymczak, Ângela Castela, Sandra Marín-Cañas, Bianca Marmontel de Souza, Ioannis Gkantounas, Maikel Colli, Federica Fantuzzi, Cristina Cosentino, Mariana Igoillo-Esteve, Lorella Marselli, Piero Marchetti, Miriam Cnop, Décio L Eizirik","doi":"10.1080/19382014.2021.1948282","DOIUrl":"10.1080/19382014.2021.1948282","url":null,"abstract":"Exposure of human pancreatic beta cells to pro-inflammatory cytokines or metabolic stressors is used to model events related to type 1 and type 2 diabetes, respectively. Quantitative real-time PCR is commonly used to quantify changes in gene expression. The selection of the most adequate reference gene(s) for gene expression normalization is an important pre-requisite to obtain accurate and reliable results. There are no universally applicable reference genes, and the human beta cell expression of commonly used reference genes can be altered by different stressors. Here we aimed to identify the most stably expressed genes in human beta cells to normalize quantitative real-time PCR gene expression.We used comprehensive RNA-sequencing data from the human pancreatic beta cell line EndoC-βH1, human islets exposed to cytokines or the free fatty acid palmitate in order to identify the most stably expressed genes. Genes were filtered based on their level of significance (adjusted P-value >0.05), fold-change (|fold-change| <1.5) and a coefficient of variation <10%. Candidate reference genes were validated by quantitative real-time PCR in independent samples.We identified a total of 264 genes stably expressed in EndoC-βH1 cells and human islets following cytokines - or palmitate-induced stress, displaying a low coefficient of variation. Validation by quantitative real-time PCR of the top five genes ARF1, CWC15, RAB7A, SIAH1 and VAPA corroborated their expression stability under most of the tested conditions. Further validation in independent samples indicated that the geometric mean of ACTB and VAPA expression can be used as a reliable normalizing factor in human beta cells.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"13 3-4","pages":"51-65"},"PeriodicalIF":1.7,"publicationDate":"2021-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bb/ed/KISL_13_1948282.PMC8280887.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39168737","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

Novel mouse model expands potential human α-cell research. 新型小鼠模型拓展了潜在的人类α细胞研究。

IF 2.2 4区医学

Islets Pub Date : 2021-07-04 Epub Date: 2021-04-14 DOI: 10.1080/19382014.2021.1914507

Theodore Dos Santos, Patrick E MacDonald

引用次数: 0

Evidence for the existence and potential roles of intra-islet glucagon-like peptide-1. 胰岛内胰高血糖素样肽-1存在及其潜在作用的证据。

IF 2.2 4区医学

Islets Pub Date : 2021-03-04 Epub Date: 2021-03-16 DOI: 10.1080/19382014.2021.1889941

Scott A Campbell, Janyne Johnson, Peter E Light

{"title":"Evidence for the existence and potential roles of intra-islet glucagon-like peptide-1.","authors":"Scott A Campbell, Janyne Johnson, Peter E Light","doi":"10.1080/19382014.2021.1889941","DOIUrl":"https://doi.org/10.1080/19382014.2021.1889941","url":null,"abstract":"Glucagon-Like Peptide-1 (GLP-1) is an important peptide hormone secreted by L-cells in the gastrointestinal tract in response to nutrients. It is produced by the differential cleavage of the proglucagon peptide. GLP-1 elicits a wide variety of physiological responses in many tissues that contribute to metabolic homeostasis. For these reasons, therapies designed to either increase endogenous GLP-1 levels or introduce exogenous peptide mimetics are now widely used in the management of diabetes. In addition to GLP-1 production from L-cells, recent reports suggest that pancreatic islet alpha cells may also synthesize and secrete GLP-1. Intra-islet GLP-1 may therefore play an unappreciated role in islet health and glucose regulation, suggesting a potential functional paracrine role for islet-derived GLP-1. In this review, we assess the current literature from an islet-centric point-of-view to better understand the production, degradation, and actions of GLP-1 within the endocrine pancreas in rodents and humans. The relevance of intra-islet GLP-1 in human physiology is discussed regarding the potential role of intra-islet GLP-1 in islet health and dysfunction.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"13 1-2","pages":"32-50"},"PeriodicalIF":2.2,"publicationDate":"2021-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2021.1889941","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25482410","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: 6

Protein kinase C-θ knockout decreases serum IL-10 levels and inhibits insulin secretion from islet β cells. 蛋白激酶C-θ敲除可降低血清IL-10水平，抑制胰岛β细胞分泌胰岛素。

IF 2.2 4区医学

Islets Pub Date : 2021-03-04 Epub Date: 2021-03-09 DOI: 10.1080/19382014.2021.1890963

Feng Hong, Yang Yang, Baiyi Chen, Peng Li, Guoguang Wang, Yuxin Jiang

{"title":"Protein kinase C-θ knockout decreases serum IL-10 levels and inhibits insulin secretion from islet β cells.","authors":"Feng Hong, Yang Yang, Baiyi Chen, Peng Li, Guoguang Wang, Yuxin Jiang","doi":"10.1080/19382014.2021.1890963","DOIUrl":"https://doi.org/10.1080/19382014.2021.1890963","url":null,"abstract":"Various subtypes of protein kinase C (PKC) are expressed in islet β cells and regulate β cell proliferation and survival. PKC-θ is distributed in the immune system and promotes the secretion of IL-10, which manifests a critical role in the onset of diabetes, by the immune cells. However, the role of PKC-θ in islets has not been concerned. In the present study, we investigated the role of PKC-θ in the protection of islet β cells and insulin secretion. Fasting glucose and insulin measurement, glucose tolerant test, immunofluorescence, and ELISA were conducted to study the influence of PKC-θ knockout on islet β cell survival and function, and explore the mechanism underlying this regulation. PKC-θ knockout mice at 2 weeks manifested normal serum insulin levels, glucose tolerance, and β cell mass. Knockout mice at 8 weeks show decreased β cell mass, but manifested normal insulin levels and glucose tolerance. Knockout mice at 16 weeks manifested impaired glucose tolerance, β cell mass, and decreased glucose stimulated insulin secretion. Furthermore, knockout mice manifested decreased serum IL-10 level compared with normal mice since 2 weeks. IL-10 injection into knockout mice improved glucose tolerance, serum insulin level, and reduced β cell mass, and IL-10 administration into cultured pancreatic tissue increased glucose stimulated insulin secretion. PKC-θ knockout decreases the secretion of IL-10, reduces β cell mass and insulin secretion in pancreatic islets. The present study illuminates the critical role of PKC-θ in protecting the survival and function of islet β cells.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"13 1-2","pages":"24-31"},"PeriodicalIF":2.2,"publicationDate":"2021-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2021.1890963","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25479118","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

Failure mode and effect analysis in human islet isolation: from the theoretical to the practical risk. 人胰岛隔离的失效模式及影响分析:从理论风险到实践风险。

IF 2.2 4区医学

Islets Pub Date : 2021-03-04 Epub Date: 2021-02-22 DOI: 10.1080/19382014.2020.1856618

Quentin Perrier, Vanessa Lavallard, Nadine Pernin, Charles-Henri Wassmer, David Cottet-Dumoulin, Fanny Lebreton, Kevin Bellofatto, Axel Andres, Ekaterine Berishvili, Domenico Bosco, Thierry Berney, Géraldine Parnaud

{"title":"Failure mode and effect analysis in human islet isolation: from the theoretical to the practical risk.","authors":"Quentin Perrier, Vanessa Lavallard, Nadine Pernin, Charles-Henri Wassmer, David Cottet-Dumoulin, Fanny Lebreton, Kevin Bellofatto, Axel Andres, Ekaterine Berishvili, Domenico Bosco, Thierry Berney, Géraldine Parnaud","doi":"10.1080/19382014.2020.1856618","DOIUrl":"https://doi.org/10.1080/19382014.2020.1856618","url":null,"abstract":"This study aimed to assess the global mapping risk of human islet isolation, using a failure mode and effect analysis (FMEA), and highlight the impact of quality assurance procedures on the risk level of criticality. Risks were scored using the risk priority number (RPN) scoring method. The risk level of criticality was made based on RPN and led to risk classification (low to critical). A raw risk analysis and a risk control analysis (with control means and quality assurance performance) were undertaken. The process of human islet isolation was divided into 11 steps, and 230 risks were identified. Analysis of the highest RPN of each of the 11 steps showed that the 4 highest risks were related to the pancreas digestion and islet purification stages. After implementation of reduction measures and controls, critical and severe risks were reduced by 3-fold and by 2-fold, respectively, so that 90% of risks could be considered as low to moderate. FMEA has proven to be a powerful approach for the identification of weaknesses in the islet isolation processes. The results demonstrated the importance of staff qualification and continuous training and supported the contribution of the quality assurance system to risk reduction.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"13 1-2","pages":"1-9"},"PeriodicalIF":2.2,"publicationDate":"2021-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1856618","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25392819","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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