IF 2.2 4区医学

Islets Pub Date : 2018-01-01 Epub Date: 2018-10-12 DOI: 10.1080/19382014.2018.1513748

Nidheesh Dadheech, Dominique Garrel, Jean Buteau

{"title":"Evidence of unrestrained beta-cell proliferation and neogenesis in a patient with hyperinsulinemic hypoglycemia after gastric bypass surgery.","authors":"Nidheesh Dadheech, Dominique Garrel, Jean Buteau","doi":"10.1080/19382014.2018.1513748","DOIUrl":"https://doi.org/10.1080/19382014.2018.1513748","url":null,"abstract":"Hyperinsulinemic hypoglycemia syndrome (HIHG) is a rare complication of roux-en-Y gastric bypass surgery. The pathology is associated with an excessive function of pancreatic beta-cells, and requires pancreas resection in patients that are recalcitrant to nutritional and pharmacological interventions. The exact prevalence is not clearly understood and the underlying mechanisms not yet fully characterized. We herein sought to perform histological and molecular examination of pancreatic sections obtained from a patient who developed HIHG as a complication of gastric bypass compared to 3 weight-matched controls. We studied markers of cellular replication and beta-cell differentiation by immunohistochemistry and immunofluorescence. HIHG after gastric bypass was characterized by a profound increase in beta-cell mass. Cellular proliferation was increased in islets and ducts compared to controls, suggesting unrestrained proliferation in HIHG. We also detected beta-cell differentiation markers in duct cells and occasional duct cells displaying both insulin and glucagon immunoreactivity. These histological observations suggest that beta-cell differentiation from ductal progenitor cells could also underly beta-cell mass expansion in HIHG. Altogether, our results can be construed to demonstrate that HIHG after gastric bypass is characterized by abnormal beta-cell mass expansion, resulting from both unrestrained beta-cell replication and neogenesis.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"10 6","pages":"213-220"},"PeriodicalIF":2.2,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2018.1513748","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36567447","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

In vivo monitoring of intracellular Ca²⁺ dynamics in the pancreatic β-cells of zebrafish embryos. 斑马鱼胚胎胰腺β细胞胞内Ca2+动态的体内监测。

IF 2.2 4区医学

Islets Pub Date : 2018-01-01 Epub Date: 2018-12-06 DOI: 10.1080/19382014.2018.1540234

Reka Lorincz, Christopher H Emfinger, Andrea Walcher, Michael Giolai, Claudia Krautgasser, Maria S Remedi, Colin G Nichols, Dirk Meyer

{"title":"In vivo monitoring of intracellular Ca2+ dynamics in the pancreatic β-cells of zebrafish embryos.","authors":"Reka Lorincz, Christopher H Emfinger, Andrea Walcher, Michael Giolai, Claudia Krautgasser, Maria S Remedi, Colin G Nichols, Dirk Meyer","doi":"10.1080/19382014.2018.1540234","DOIUrl":"https://doi.org/10.1080/19382014.2018.1540234","url":null,"abstract":"Assessing the response of pancreatic islet cells to glucose stimulation is important for understanding β-cell function. Zebrafish are a promising model for studies of metabolism in general, including stimulus-secretion coupling in the pancreas. We used transgenic zebrafish embryos expressing a genetically-encoded Ca2+ sensor in pancreatic β-cells to monitor a key step in glucose induced insulin secretion; the elevations of intracellular [Ca2+]i. In vivo and ex vivo analyses of [Ca2+]i demonstrate that β-cell responsiveness to glucose is well established in late embryogenesis and that embryonic β-cells also respond to free fatty acid and amino acid challenges. In vivo imaging of whole embryos further shows that indirect glucose administration, for example by yolk injection, results in a slow and asynchronous induction of β-cell [Ca2+]i responses, while intravenous glucose injections cause immediate and islet-wide synchronized [Ca2+]i fluctuations. Finally, we demonstrate that embryos with disrupted mutation of the CaV1.2 channel gene cacna1c are hyperglycemic and that this phenotype is associated with glucose-independent [Ca2+]i fluctuation in β-cells. The data reveal a novel central role of cacna1c in β-cell specific stimulus-secretion coupling in zebrafish and demonstrate that the novel approach we propose - to monitor the [Ca2+]i dynamics in embryonic β-cells in vivo - will help to expand the understanding of β-cell physiological functions in healthy and diseased states.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"10 6","pages":"221-238"},"PeriodicalIF":2.2,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2018.1540234","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36755863","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: 13

Direct comparison of the abilities of bone marrow mesenchymal versus hematopoietic stem cells to reverse hyperglycemia in diabetic NOD.SCID mice. 骨髓间充质干细胞与造血干细胞逆转糖尿病性NOD高血糖能力的直接比较SCID小鼠。

IF 2.2 4区医学

Islets Pub Date : 2018-01-01 Epub Date: 2018-08-15 DOI: 10.1080/19382014.2018.1480285

Edith J Arany, Muhammad Waseem, Brenda J Strutt, Astrid Chamson-Reig, Adam Bernardo, Elizabeth Eng, David J Hill

{"title":"Direct comparison of the abilities of bone marrow mesenchymal versus hematopoietic stem cells to reverse hyperglycemia in diabetic NOD.SCID mice.","authors":"Edith J Arany, Muhammad Waseem, Brenda J Strutt, Astrid Chamson-Reig, Adam Bernardo, Elizabeth Eng, David J Hill","doi":"10.1080/19382014.2018.1480285","DOIUrl":"https://doi.org/10.1080/19382014.2018.1480285","url":null,"abstract":"Both bone marrow-derived hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) improve glycemic control in diabetic mice, but their kinetics and associated changes in pancreatic morphology have not been directly compared. Our goal was to examine the time course of improvements in glucose tolerance and associated changes in β-cell mass and proliferation following transplantation of equivalent numbers of HSC or MSC from the same bone marrow into diabetic non-obese diabetic severe combined immune deficiency (NOD.SCID) mice. We used transgenic mice with a targeted expression of yellow fluorescent protein (YFP) driven by the Vav1 gene promoter to genetically tag HSC and progeny. HSC were separated from bone marrow by fluorescence-activated cell sorting and MSC following cell culture. Equivalent numbers of isolated HSC or MSC were transplanted directly into the pancreas of NOD.SCID mice previously made diabetic with streptozotocin. Glucose tolerance, serum insulin, β-cell mass and β-cell proliferation were examined up to 28 days following transplant. Transplantation with MSC improved glucose tolerance within 7 days and serum insulin levels increased, but with no increase in β-cell mass. Mice transplanted with HSC showed improved glucose tolerance only after 3 weeks associated with increased β-cell proliferation and mass. We conclude that single injections of either MSC or HSC transiently improved glycemic control in diabetic NOD.SCID mice, but with different time courses. However, only HSC infiltrated the islets and were associated with an expanded β-cell mass. This suggests that MSC and HSC have differing mechanisms of action.","PeriodicalId":14671,"journal":{"name":"Islets","volume":" ","pages":"137-150"},"PeriodicalIF":2.2,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2018.1480285","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36400876","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

Patient and family expectations of beta-cell replacement therapies in type 1 diabetes. 1型糖尿病患者和家属对β细胞替代疗法的期望

IF 2.2 4区医学

Islets Pub Date : 2018-01-01 Epub Date: 2018-08-17 DOI: 10.1080/19382014.2018.1503518

Akitsu Kawabe, Shinichi Matsumoto, Masayuki Shimoda

{"title":"Patient and family expectations of beta-cell replacement therapies in type 1 diabetes.","authors":"Akitsu Kawabe, Shinichi Matsumoto, Masayuki Shimoda","doi":"10.1080/19382014.2018.1503518","DOIUrl":"https://doi.org/10.1080/19382014.2018.1503518","url":null,"abstract":"Background: New methods of beta-cell replacement have been developed to maintain excellent glycemic control, improve quality of life, and even eliminate insulin injections in patients with type 1 diabetes mellitus (T1DM). Previously, we demonstrated that being insulin-free is the strongest motivation for accepting a newly developed therapy. Multiple allogeneic islet transplantations with immunosuppression using a human donor is the best option to be insulin-free, but the necessity for immunosuppression and donor shortage are major issues. However, these issues have been improved with scientific progress. The aim of this study was to investigate the opinions of patients and their families about the current progress.Methods: We conducted a questionnaire survey of T1DM patients (n = 47) and their family members (n = 49) about newly developed therapies: single and multiple allogeneic islet transplantation, single and multiple encapsulated allogeneic islet transplantation, single and multiple xenogeneic islet transplantation, and induced pluripotent stem cell therapy.Results: More than 90% of respondents wished to be insulin-free and have stable glycemic control. More than 90% of respondents accepted at least one of the new therapies. The current standard treatment multiple allogeneic islet transplantation was not well accepted or favored.Conclusions: The next generation of treatments, including xenotransplantation and induced pluripotent stem cell therapy, were more acceptable and favorable. Even though the majority of patients wish to become insulin-free, it is not sufficiently strong motivation for accepting newly developed treatments.","PeriodicalId":14671,"journal":{"name":"Islets","volume":" ","pages":"190-200"},"PeriodicalIF":2.2,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2018.1503518","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40442558","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

Over ten-year insulin independence following single allogeneic islet transplant without T-cell depleting antibody induction. 在没有t细胞消耗抗体诱导的单一异体胰岛移植后，超过十年的胰岛素依赖性。

IF 2.2 4区医学

Islets Pub Date : 2018-01-01 Epub Date: 2018-07-19 DOI: 10.1080/19382014.2018.1451281

Jack Williams, Nicholas Jacus, Kevin Kavalackal, Kirstie K Danielson, Rebecca S Monson, Yong Wang, Jose Oberholzer

引用次数: 7

Beta-cell hubs maintain Ca²⁺ oscillations in human and mouse islet simulations. β细胞中心维持Ca2+振荡在人类和小鼠胰岛模拟。

IF 1.9 4区医学

Islets Pub Date : 2018-01-01 DOI: 10.1080/19382014.2018.1493316

Chon-Lok Lei, Joely A Kellard, Manami Hara, James D Johnson, Blanca Rodriguez, Linford J B Briant

{"title":"Beta-cell hubs maintain Ca2+ oscillations in human and mouse islet simulations.","authors":"Chon-Lok Lei, Joely A Kellard, Manami Hara, James D Johnson, Blanca Rodriguez, Linford J B Briant","doi":"10.1080/19382014.2018.1493316","DOIUrl":"10.1080/19382014.2018.1493316","url":null,"abstract":"Islet β-cells are responsible for secreting all circulating insulin in response to rising plasma glucose concentrations. These cells are a phenotypically diverse population that express great functional heterogeneity. In mice, certain β-cells (termed 'hubs') have been shown to be crucial for dictating the islet response to high glucose, with inhibition of these hub cells abolishing the coordinated Ca2+ oscillations necessary for driving insulin secretion. These β-cell hubs were found to be highly metabolic and susceptible to pro-inflammatory and glucolipotoxic insults. In this study, we explored the importance of hub cells in human by constructing mathematical models of Ca2+ activity in human islets. Our simulations revealed that hubs dictate the coordinated Ca2+ response in both mouse and human islets; silencing a small proportion of hubs abolished whole-islet Ca2+ activity. We also observed that if hubs are assumed to be preferentially gap junction coupled, then the simulations better adhere to the available experimental data. Our simulations of 16 size-matched mouse and human islet architectures revealed that there are species differences in the role of hubs; Ca2+ activity in human islets was more vulnerable to hub inhibition than mouse islets. These simulation results not only substantiate the existence of β-cell hubs, but also suggest that hubs may be favorably coupled in the electrical and metabolic network of the islet, and that targeted destruction of these cells would greatly impair human islet function.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"10 4","pages":"151-167"},"PeriodicalIF":1.9,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10055474","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

Neprilysin inhibition in mouse islets enhances insulin secretion in a GLP-1 receptor dependent manner. Neprilysin抑制小鼠胰岛以GLP-1受体依赖的方式增强胰岛素分泌。

IF 2.2 4区医学

Islets Pub Date : 2018-01-01 Epub Date: 2018-08-24 DOI: 10.1080/19382014.2018.1502521

Nathalie Esser, Breanne M Barrow, Edwina Choung, Nancy J Shen, Sakeneh Zraika

{"title":"Neprilysin inhibition in mouse islets enhances insulin secretion in a GLP-1 receptor dependent manner.","authors":"Nathalie Esser, Breanne M Barrow, Edwina Choung, Nancy J Shen, Sakeneh Zraika","doi":"10.1080/19382014.2018.1502521","DOIUrl":"https://doi.org/10.1080/19382014.2018.1502521","url":null,"abstract":"Neprilysin, a widely expressed peptidase upregulated in type 2 diabetes, is capable of cleaving and inactivating the insulinotropic glucagon-like peptide-1 (GLP-1). Like dipeptidyl peptidase-4 (DPP-4), inhibition of neprilysin activity under diabetic conditions is associated with increased active GLP-1 levels and improved glycemic control. While neprilysin expression has been demonstrated in islets, its local contribution to GLP-1-mediated insulin secretion remains unknown. We investigated in vitro whether islet neprilysin inhibition enhances insulin secretion in response to glucose and/or exogenous GLP-1, and whether these effects are mediated by GLP-1 receptor (GLP-1R). Further, we compared the effect of neprilysin versus DPP-4 inhibition on insulin secretion. Isolated islets from wild-type (Glp1r+/+) and GLP-1 receptor knockout (Glp1r-/-) mice were incubated with or without the neprilysin inhibitor thiorphan and/or the DPP-4 inhibitor sitagliptin for 2.5 hours. During the last hour, insulin secretion was assessed in response to 2.8 mmol/l or 20 mmol/l glucose alone or plus exogenous active GLP-1. In Glp1r+/+ islets, neprilysin inhibition enhanced 2.8 mmol/l and 20 mmol/l glucose- and GLP-1-mediated insulin secretion to the same extent as DPP-4 inhibition. These effects were blunted in Glp1r-/- islets. In conclusion, inhibition of islet neprilysin in vitro increases glucose-mediated insulin secretion in a GLP-1R-dependent manner and enhances the insulinotropic effect of exogenous active GLP-1. Thus, neprilysin inhibitors may have therapeutic potential in type 2 diabetes by preserving islet-derived and circulating active GLP-1 levels.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"10 5","pages":"175-180"},"PeriodicalIF":2.2,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2018.1502521","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36424663","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: 18

The triggering pathway to insulin secretion: Functional similarities and differences between the human and the mouse β cells and their translational relevance. 胰岛素分泌的触发途径：人类和小鼠β细胞在功能上的异同及其转化意义。

IF 2.2 4区医学

Islets Pub Date : 2017-11-02 Epub Date: 2017-06-29 DOI: 10.1080/19382014.2017.1342022

Maša Skelin Klemen, Jurij Dolenšek, Marjan Slak Rupnik, Andraž Stožer

{"title":"The triggering pathway to insulin secretion: Functional similarities and differences between the human and the mouse β cells and their translational relevance.","authors":"Maša Skelin Klemen, Jurij Dolenšek, Marjan Slak Rupnik, Andraž Stožer","doi":"10.1080/19382014.2017.1342022","DOIUrl":"10.1080/19382014.2017.1342022","url":null,"abstract":"In β cells, stimulation by metabolic, hormonal, neuronal, and pharmacological factors is coupled to secretion of insulin through different intracellular signaling pathways. Our knowledge about the molecular machinery supporting these pathways and the patterns of signals it generates comes mostly from rodent models, especially the laboratory mouse. The increased availability of human islets for research during the last few decades has yielded new insights into the specifics in signaling pathways leading to insulin secretion in humans. In this review, we follow the most central triggering pathway to insulin secretion from its very beginning when glucose enters the β cell to the calcium oscillations it produces to trigger fusion of insulin containing granules with the plasma membrane. Along the way, we describe the crucial building blocks that contribute to the flow of information and focus on their functional role in mice and humans and on their translational implications.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"9 6","pages":"109-139"},"PeriodicalIF":2.2,"publicationDate":"2017-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/59/83/kisl-09-06-1342022.PMC5710702.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35129472","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

Effectiveness of different molecular forms of C. histolyticum class I collagenase to recover islets. 不同分子形式溶组织梭菌I类胶原酶对胰岛恢复的效果。

IF 2.2 4区医学

Islets Pub Date : 2017-11-02 Epub Date: 2017-09-21 DOI: 10.1080/19382014.2017.1365996

Michael L Green, Andrew G Breite, Caleb A Beechler, Francis E Dwulet, Robert C McCarthy

引用次数: 4

Effect of liver histopathology on islet cell engraftment in the model mimicking autologous islet cell transplantation. 肝脏组织病理学对模拟自体胰岛细胞移植模型中胰岛细胞移植的影响。

IF 2.2 4区医学

Islets Pub Date : 2017-11-02 Epub Date: 2017-09-13 DOI: 10.1080/19382014.2017.1356558

Chirag S Desai, Khalid M Khan, Xiaobo Ma, Henghong Li, Juan Wang, Lijuan Fan, Guoling Chen, Jill P Smith, Wanxing Cui

{"title":"Effect of liver histopathology on islet cell engraftment in the model mimicking autologous islet cell transplantation.","authors":"Chirag S Desai, Khalid M Khan, Xiaobo Ma, Henghong Li, Juan Wang, Lijuan Fan, Guoling Chen, Jill P Smith, Wanxing Cui","doi":"10.1080/19382014.2017.1356558","DOIUrl":"https://doi.org/10.1080/19382014.2017.1356558","url":null,"abstract":"Background: The inflammatory milieu in the liver as determined by histopathology is different in individual patients undergoing autologous islet cell transplantation. We hypothesized that inflammation related to fatty-liver adversely impacts islet survival. To test this hypothesis, we used a mouse model of fatty-liver to determine the outcome of syngeneic islet transplantation after chemical pancreatectomy.Methods: Mice (C57BL/6) were fed a high-fat-diet from 6 weeks of age until attaining a weight of ≥28 grams (6-8 weeks) to produce a fatty liver (histologically > 30% fat);steatosis was confirmed with lipidomic profile of liver tissue. Islets were infused via the intra-portal route in fatty-liver and control mice after streptozotocin induction of diabetes. Outcomes were assessed by the rate of euglycemia, liver histopathology, evaluation of liver inflammation by measuring tissue cytokines IL-1β and TNF-α by RT-PCR and CD31 expression by immunohistochemistry.Results: The difference in the euglycemic fraction between the normal liver group (90%, 9/10) and the fatty-liver group (37.5%, 3/8) was statistically significant at the 18th day post- transplant and was maintained to the end of the study (day 28) (p = 0.019, X2 = 5.51). Levels of TNF-α and IL-1β were elevated in fatty-liver mice (p = 0.042, p = 0.037). Compared to controls cytokine levels were elevated after islet cell transplantation and in transplanted fatty-liver mice as compared to either fatty- or islet transplant group alone (p = NS). A difference in the histochemical pattern of CD31 could not be determined.Conclusion: Fatty-liver creates an inflammatory state which adversely affects the outcome of autologous islet cell transplantation.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"9 6","pages":"140-149"},"PeriodicalIF":2.2,"publicationDate":"2017-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2017.1356558","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35507631","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: 11

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