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Characterization of pre-transplant psychosocial burden in an integrated national islet transplant program. 国家综合胰岛移植计划中移植前心理社会负担的特征。
IF 2.2 4区 医学
Islets Pub Date : 2020-03-03 Epub Date: 2020-08-20 DOI: 10.1080/19382014.2020.1736740
Aaron Yl Liew, Elizabeth Holmes-Truscott, Anneliese Js Flatt, Denise Bennett, Robert Crookston, Mirka Pimkova, Linda Birtles, John Casey, Andrew Pernet, Ruth C Wood, Pratik Choudhary, Shareen Forbes, Martin K Rutter, Miranda Rosenthal, Paul Johnson, James Am Shaw, Jane Speight
{"title":"Characterization of pre-transplant psychosocial burden in an integrated national islet transplant program.","authors":"Aaron Yl Liew,&nbsp;Elizabeth Holmes-Truscott,&nbsp;Anneliese Js Flatt,&nbsp;Denise Bennett,&nbsp;Robert Crookston,&nbsp;Mirka Pimkova,&nbsp;Linda Birtles,&nbsp;John Casey,&nbsp;Andrew Pernet,&nbsp;Ruth C Wood,&nbsp;Pratik Choudhary,&nbsp;Shareen Forbes,&nbsp;Martin K Rutter,&nbsp;Miranda Rosenthal,&nbsp;Paul Johnson,&nbsp;James Am Shaw,&nbsp;Jane Speight","doi":"10.1080/19382014.2020.1736740","DOIUrl":"https://doi.org/10.1080/19382014.2020.1736740","url":null,"abstract":"<p><p>The psychological burden experienced by people with diabetes prior to islet transplantation is recognized but has not been studied comprehensively, especially in relation to glycemia. Therefore, we conducted a rigorous pre-operative psychosocial profile of UK islet transplant recipients, and compared groups with higher/lower HbA1 c to test the null hypothesis that pre-transplant hypoglycemia awareness and psychosocial burden would not be related to baseline HbA1 c in this high-risk cohort. Pre-transplant, recipients (n = 44) completed validated hypoglycemia awareness questionnaires and generic/diabetes-specific measures of psychological traits and states. Scores were compared in groups, dichotomized by HbA1 c (≤8% versus >8%). Participants were aged (mean±SD) 53 ± 10 years; 64% were women; with HbA1 c 8.3 ± 1.7%. Median rate of severe hypoglycemia over the preceding 12 months was 13 events/person-year and 90% had impaired awareness of hypoglycemia (Gold/Clarke score ≥4). Participants had elevated fear of hypoglycemia (HFS-II Worry), impaired diabetes-specific quality of life (DQoL) and low generic health status (SF-36; EQ-5D). One quarter reported scores indicating likely anxiety/depression (HAD). Dispositional optimism (LOT-R) and generalized self-efficacy (GSE) were within published 'norms.' Despite negative perceptions of diabetes (including low personal control), participants were confident that islet transplantation would help (BIPQ). Hypoglycemia awareness and psychosocial profile were comparable in lower (n = 24) and higher (n = 20) HbA1 c groups. Islet transplant candidates report sub-optimal generic psychological states (anxiety/depressive symptoms), health status and diabetes-specific psychological states (fear of hypoglycemia, diabetes-specific quality of life). While their generic psychological traits (optimism, self-efficacy) are comparable with the general population, they are highly optimistic about forthcoming transplant. HbA1 c is not a proxy measure of psychosocial burden, which requires the use of validated questionnaires to systematically identify those who may benefit most from psychological assessment and support.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 2","pages":"21-31"},"PeriodicalIF":2.2,"publicationDate":"2020-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1736740","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38279081","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
Pancreatic and duodenal homeobox-1 (PDX1) contributes to β-cell mass expansion and proliferation induced by Akt/PKB pathway. 胰腺和十二指肠同源盒-1 (PDX1)参与Akt/PKB通路诱导的β细胞团扩增和增殖。
IF 2.2 4区 医学
Islets Pub Date : 2020-03-03 DOI: 10.1080/19382014.2020.1762471
Mark Anthony Jara, Joao Pedro Werneck-De-Castro, Camila Lubaczeuski, James D Johnson, Ernesto Bernal-Mizrachi
{"title":"Pancreatic and duodenal homeobox-1 (PDX1) contributes to β-cell mass expansion and proliferation induced by Akt/PKB pathway.","authors":"Mark Anthony Jara,&nbsp;Joao Pedro Werneck-De-Castro,&nbsp;Camila Lubaczeuski,&nbsp;James D Johnson,&nbsp;Ernesto Bernal-Mizrachi","doi":"10.1080/19382014.2020.1762471","DOIUrl":"https://doi.org/10.1080/19382014.2020.1762471","url":null,"abstract":"<p><p>Maintenance of pancreatic β-cell mass and function is fundamental to glucose homeostasis and to prevent diabetes. The PI3 K-Akt-mTORC1 pathway is critical for β-cells mass and function, while PDX1 has been implicated in β-cell development, maturation, and function. Here we tested whether Akt signaling requires PDX1 expression to regulate β-cell mass, proliferation, and glucose homeostasis. In order to address that, we crossed a mouse model overexpressing constitutively active Akt mutant in β-cells (<i>β-caAkt</i>) with mice lacking one allele of PDX1gene (<i>β-caAkt/pdx1<sup>+/-</sup>)</i>. While the <i>β-caAkt</i> mice exhibit higher plasma insulin levels, greater β-cell mass and improved glucose tolerance compared to control mice, the <i>β-caAkt/pdx1<sup>+/-</sup></i> mice are hyperglycemic and intolerant to glucose. The changes in glucose homeostasis in <i>β-caAkt/pdx1<sup>+/-</sup></i> were associated with a 60% reduction in β-cell mass compared to <i>β-caAkt</i> mice. The impaired β-cell mass in the <i>β-caAkt/pdx1<sup>+/-</sup></i> mice can be explained by a lesser β-cell proliferation measured by the number of Ki67 positive β-cells. We did not observe any differences in apoptosis between <i>β-caAkt/pdx1<sup>+/-</sup></i> and <i>β-caAkt</i> mice. In conclusion, PDX1 contributes to β-cell mass expansion and glucose metabolism induced by activation of Akt signaling.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 2","pages":"32-40"},"PeriodicalIF":2.2,"publicationDate":"2020-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2020.1762471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38336301","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: 19
The effect of preexisting HMGB1 within fetal bovine serum on murine pancreatic beta cell biology. 胎牛血清中预先存在的HMGB1对小鼠胰腺β细胞生物学的影响。
IF 2.2 4区 医学
Islets Pub Date : 2020-01-01 Epub Date: 2020-01-14 DOI: 10.1080/19382014.2019.1696128
Hyunwoo Chung, Sung Ji Hong, So Won Choi, Chung-Gyu Park
{"title":"The effect of preexisting HMGB1 within fetal bovine serum on murine pancreatic beta cell biology.","authors":"Hyunwoo Chung,&nbsp;Sung Ji Hong,&nbsp;So Won Choi,&nbsp;Chung-Gyu Park","doi":"10.1080/19382014.2019.1696128","DOIUrl":"https://doi.org/10.1080/19382014.2019.1696128","url":null,"abstract":"<p><p>High-mobility group box 1 (HMGB1) can act as a structural protein of the chromatin and at the same time as a mediator of the immune system. Its high correlation with the graft acceptance in pancreatic islet recipients makes it a biomarker in islet transplantation. With the suspicion that preexisting HMGB1 in the fetal bovine serum (FBS) would be detrimental to the viability and function of murine beta cells, HMGB1 was removed from FBS and its impact was investigated. Interestingly, the elimination of HMGB1 from FBS seemed unfavorable to the viability and function of cultured murine beta cells, suggesting that the preexisting HMGB1 in the FBS may be an indispensable component of islet cell culture.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 1","pages":"1-8"},"PeriodicalIF":2.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2019.1696128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37540515","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
Inflammatory biomarkers in the blood and pancreatic tissue of organ donors that predict human islet isolation success and function. 预测人类胰岛分离成功和功能的器官供体血液和胰腺组织中的炎症生物标志物。
IF 2.2 4区 医学
Islets Pub Date : 2020-01-01 Epub Date: 2020-01-14 DOI: 10.1080/19382014.2019.1696127
Alina R Oancea, Keiko Omori, Chris Orr, Jeffrey Rawson, Donald C Dafoe, Ismail H Al-Abdullah, Fouad Kandeel, Yoko Mullen
{"title":"Inflammatory biomarkers in the blood and pancreatic tissue of organ donors that predict human islet isolation success and function.","authors":"Alina R Oancea,&nbsp;Keiko Omori,&nbsp;Chris Orr,&nbsp;Jeffrey Rawson,&nbsp;Donald C Dafoe,&nbsp;Ismail H Al-Abdullah,&nbsp;Fouad Kandeel,&nbsp;Yoko Mullen","doi":"10.1080/19382014.2019.1696127","DOIUrl":"https://doi.org/10.1080/19382014.2019.1696127","url":null,"abstract":"<p><p>The pancreas of brain-dead donors is the primary source of islets for transplantation. However, brain death mediates systemic inflammation, which may affect the quantity and quality of isolated islets. Our aim was to identify inflammatory biomarkers in donor blood and/or pancreatic tissue capable of predicting islet isolation success. Blood samples were collected from 21 pancreas donors and 14 healthy volunteers. Pancreatic tissue samples were also collected from the corresponding donor during organ procurement. Six serum cytokines were measured by a fluorescent bead-based immunoassay, and the expression of fifteen inflammatory target genes was quantified by quantitative reverse transcription polymerase chain reaction (RT-qPCR). There was no correlation between serum inflammatory cytokines and mRNA expression of the corresponding genes in peripheral blood mononuclear cells (PBMCs) or pancreatic tissue. The <i>IL6</i> expression in pancreatic tissue correlated negatively with post-isolation islet yield. Islets isolated from donors highly expressing <i>IFNG</i> in PBMCs and <i>MAC1</i> in pancreatic tissue functioned poorly <i>in vivo</i> when transplanted in diabetic NOD<i>scid</i> mice. Furthermore, the increased <i>MAC1</i> in pancreatic tissue was positively correlated with donor hospitalization time. Brain death duration positively correlated with higher expression of <i>IL1B</i> in PBMCs and <i>TNF</i> in both PBMCs and pancreatic tissue but failed to show a significant correlation with islet yield and <i>in vivo</i> function. The study indicates that the increased inflammatory genes in donor pancreatic tissues may be considered as biomarkers associated with poor islet isolation outcome.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"12 1","pages":"9-19"},"PeriodicalIF":2.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2019.1696127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37541109","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
Regional variation of human pancreatic islets dimension and its impact on beta cells in Indian population 人胰岛尺寸的区域差异及其对印度人群β细胞的影响
IF 2.2 4区 医学
Islets Pub Date : 2019-11-02 DOI: 10.1080/19382014.2019.1686323
P. Ravi, S. Purkait, Usha Agrawal, S. Patra, Madhumita Patnaik, S. Singh, P. Mishra
{"title":"Regional variation of human pancreatic islets dimension and its impact on beta cells in Indian population","authors":"P. Ravi, S. Purkait, Usha Agrawal, S. Patra, Madhumita Patnaik, S. Singh, P. Mishra","doi":"10.1080/19382014.2019.1686323","DOIUrl":"https://doi.org/10.1080/19382014.2019.1686323","url":null,"abstract":"ABSTRACT Background & objectives: Islet of Langerhans, the endocrine pancreas plays a significant role in glucose metabolism. Obesity and insulin resistance are the major factors responsible for beta cell dysfunction. Asian Indian population has increased susceptibility to diabetes in spite of having lower BMI. The morphology of islets plays a significant role in beta cell function. The present study was designed for better understanding the morphology, composition and distribution of islets in different parts of the pancreas and its impact on beta cell proportion. Methods: We observed islet morphology and beta cell area proportion by Large-scale computer-assisted analysis in 20 adult human pancreases in non-diabetic Indian population. Immunohistochemical staining with anti-synaptophysin and anti-insulin antibody was used to detect islet and beta cells respectively. Whole slide images were analyzed using ImageJ software. Results: Endocrine proportion were heterogeneously increasing from head to tail with maximum islet and beta cell distribution in the tail region. Larger islets were predominately confined to the tail region. The islets in Indian population were relatively smaller in size, but they have more beta cells (20%) when compared to American population. Interpretation & conclusions: The beta cells of larger islets are functionally more active than the smaller islets via paracrine effect. Thus, reduction in the number of larger islets may be one of the probable reasons for increased susceptibility of Indians to diabetes even at lower BMI. Knowledge about the regional distribution of islets will help the surgeons to preserve the islet rich regions during surgery.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"11 1","pages":"141 - 151"},"PeriodicalIF":2.2,"publicationDate":"2019-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2019.1686323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42951539","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: 5
Curcumin protects islet cells from glucolipotoxicity by inhibiting oxidative stress and NADPH oxidase activity both in vitro and in vivo 姜黄素通过抑制体内外氧化应激和NADPH氧化酶活性保护胰岛细胞免受糖脂毒性
IF 2.2 4区 医学
Islets Pub Date : 2019-11-02 DOI: 10.1080/19382014.2019.1690944
Jing Li, Ning-hua Wu, Xiao Chen, Hong-guang Chen, Xiao-Song Yang, Chao Liu
{"title":"Curcumin protects islet cells from glucolipotoxicity by inhibiting oxidative stress and NADPH oxidase activity both in vitro and in vivo","authors":"Jing Li, Ning-hua Wu, Xiao Chen, Hong-guang Chen, Xiao-Song Yang, Chao Liu","doi":"10.1080/19382014.2019.1690944","DOIUrl":"https://doi.org/10.1080/19382014.2019.1690944","url":null,"abstract":"ABSTRACT Curcumin possesses medicinal properties that are beneficial in various diseases, such as heart disease, cancer, and type 2 diabetes mellitus (T2 DM). It has been proposed that pancreatic beta cell dysfunction in T2 DM is promoted by oxidative stress caused by NADPH oxidase over-activity. The aim of the present study was to evaluate the efficacy of curcumin as a protective agent against high glucose/palmitate (HP)-induced islet cell damage and in streptozotocin (STZ)-induced DM rats. INS-1 cells were exposed to HP with or without curcumin. Cell proliferation, islet cell morphological changes, reactive oxygen species production, superoxide dismutase and catalase activity, insulin levels, NADPH oxidase subunit expression, and the expression of apoptotic factors by INS-1 cells were observed. Our results show that curcumin can effectively inhibit the impairment of cell proliferation and activated oxidative stress, increase insulin levels, and reduce the high expression of NADPH oxidase subunits and apoptotic factors induced by HP in INS-1 cells. The STZ-induced DM rat model was also used to determine whether curcumin can protect islets in vivo. Our results show that curcumin significantly reduced pathological damage and increased insulin levels of islets in STZ-induced DM rats. Curcumin also successfully inhibited the high expression of NADPH oxidase subunits and apoptotic factors in STZ-induced DM rats. These results suggest that curcumin is able to attenuate HP-induced oxidative stress in islet cells and protect these cells from apoptosis by modulating the NADPH pathway. In view of its efficiency, curcumin has potential for translation applications in protecting islets from glucolipotoxicity.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"11 1","pages":"152 - 164"},"PeriodicalIF":2.2,"publicationDate":"2019-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2019.1690944","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47786105","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: 19
A novel model for in vivo quantification of immediate liver perfusion impairment after pancreatic islet transplantation 一种新的胰岛移植后即时肝灌注损伤的体内定量模型
IF 2.2 4区 医学
Islets Pub Date : 2019-09-09 DOI: 10.1080/19382014.2019.1651164
L. Kosinová, A. Pátíková, D. Jirák, A. Gálisová, Alžběta Vojtíšková, F. Saudek, J. Kříž
{"title":"A novel model for in vivo quantification of immediate liver perfusion impairment after pancreatic islet transplantation","authors":"L. Kosinová, A. Pátíková, D. Jirák, A. Gálisová, Alžběta Vojtíšková, F. Saudek, J. Kříž","doi":"10.1080/19382014.2019.1651164","DOIUrl":"https://doi.org/10.1080/19382014.2019.1651164","url":null,"abstract":"ABSTRACT Instant Blood-Mediated Inflammatory Reaction (IBMIR) is a major cause of graft loss during pancreatic islet transplantation, leading to a low efficiency of this treatment method and significantly limiting its broader clinical use. Within the procedure, transplanted islets obstruct intrahepatic portal vein branches and consequently restrict blood supply of downstream lying liver tissue, resulting typically in ischemic necrosis. The extent of ischemic lesions is influenced by mechanical obstruction and inflammation, as well as subsequent recanalization and regeneration capacity of recipient liver tissue. Monitoring of immediate liver perfusion impairment, which is directly related to the intensity of post-transplant inflammation and thrombosis (IBMIR), is essential for improving therapeutic and preventive strategies to improve overall islet graft survival. In this study, we present a new experimental model enabling direct quantification of liver perfusion impairment after pancreatic islet transplantation using ligation of hepatic arteries followed by contrast-enhanced magnetic resonance imaging (MRI). The ligation of hepatic arteries prevents the contrast agent from circumventing the portal vein obstruction and enables to discriminate between well-perfused and non-perfused liver tissue. Here we demonstrate that the extent of liver ischemia reliably reflects the number of transplanted islets. This model represents a useful tool for in vivo monitoring of biological effect of IBMIR-alleviating interventions as well as other experiments related to liver ischemia. This technical paper introduces a novel technique and its first application in experimental animals.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"11 1","pages":"129 - 140"},"PeriodicalIF":2.2,"publicationDate":"2019-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2019.1651164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49319575","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: 4
JAK3 inhibitor-based immunosuppression in allogeneic islet transplantation in cynomolgus monkeys 基于JAK3抑制剂的免疫抑制在食蟹猴异基因胰岛移植中的应用
IF 2.2 4区 医学
Islets Pub Date : 2019-09-03 DOI: 10.1080/19382014.2019.1650580
Jong-Min Kim, Jun-Seop Shin, Byoung-Hoon Min, Seong-Jun Kang, Il‐Hee Yoon, Hyunwoo Chung, Jiyeon Kim, E. Hwang, J. Ha, Chung-Gyu Park
{"title":"JAK3 inhibitor-based immunosuppression in allogeneic islet transplantation in cynomolgus monkeys","authors":"Jong-Min Kim, Jun-Seop Shin, Byoung-Hoon Min, Seong-Jun Kang, Il‐Hee Yoon, Hyunwoo Chung, Jiyeon Kim, E. Hwang, J. Ha, Chung-Gyu Park","doi":"10.1080/19382014.2019.1650580","DOIUrl":"https://doi.org/10.1080/19382014.2019.1650580","url":null,"abstract":"ABSTRACT Islet transplantation is efficacious to prevent severe hypoglycemia and glycemic liability of selected patients of type 1 diabetes. However, since calcineurin inhibitor (CNI) causes β-cell and nephrotoxicity, alternative drug(s) with similar potency and safety profile to CNI will be highly desirable. Here we tested whether JAK3 inhibitor, tofacitinib could be used instead of tacrolimus in CIT07 immunosuppression regimen in cynomolgus nonhuman primate (NHP) model. Five independent streptozotocin (STZ)-induced diabetic monkeys were transplanted with MHC-mismatched allogeneic islets and three animals were further re-transplanted upon insufficient glycemic control or early islet graft rejection. After islet transplantation, blood glucose levels were quickly stabilized and maximal islet graft survival as measured by serum C-peptide concentration was >330, 98, >134, 31, or 22 days, respectively, after transplantation (median survival day; 98 days). Cellular and humoral immune responses were efficiently suppressed by JAK3 inhibitor-based immunosuppression during the follow-up periods. Although intermittent increases of the genome copy number of cynomolgus cytomegalovirus (CMV) were detected by quantitative real-time PCR analyses, serious infections or posttransplant lymphoproliferative disease (PTLD) was not found in all animals. Taken together, we have shown that JAK3 inhibitor could be used in replacement of tacrolimus in a highly translatable NHP islet transplantation model and these results suggest that JAK3 inhibitor will be potentially incorporated in human allogeneic islet transplantation.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"11 1","pages":"119 - 128"},"PeriodicalIF":2.2,"publicationDate":"2019-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2019.1650580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45091852","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: 11
Short-chain fatty acids and regulation of pancreatic endocrine secretion in mice 短链脂肪酸与小鼠胰腺内分泌分泌的调节
IF 2.2 4区 医学
Islets Pub Date : 2019-08-30 DOI: 10.1080/19382014.2019.1587976
Anne Ørgaard, S. L. Jepsen, J. Holst
{"title":"Short-chain fatty acids and regulation of pancreatic endocrine secretion in mice","authors":"Anne Ørgaard, S. L. Jepsen, J. Holst","doi":"10.1080/19382014.2019.1587976","DOIUrl":"https://doi.org/10.1080/19382014.2019.1587976","url":null,"abstract":"ABSTRACT The intestinal microbiota has been demonstrated to influence host metabolism, and has been proposed to affect the development of obesity and type 2 diabetes (T2D), possibly through short-chain fatty acids (SCFAs) produced by fermentation of dietary fiber. There are some indications that SCFAs inhibit glucose-stimulated insulin secretion (GSIS) in rodents, but research on this subject is sparse. However, it has been reported that receptors for SCFAs, free fatty acid receptor 2 (FFAR2) and FFAR3 are expressed not only on gut endocrine cells secreting GLP-1 and PYY, but also on pancreatic islet cells. We hypothesized that SCFAs might influence the endocrine secretion from pancreatic islets similar to their effects on the enteroendocrine cells. We studied this using isolated perfused mouse pancreas which responded adequately to changes in glucose and to infusions of arginine. None of the SCFAs, acetate, propionate and butyrate, influenced glucagon secretion, whereas they had weak inhibitory effects on somatostatin and insulin secretion. Infusions of two specific agonists of FFAR2 and FFAR3, CFMB and Compound 4, respectively, did not influence the pancreatic secretion of insulin and glucagon, whereas both induced strong increases in the secretion of somatostatin. In conclusion, the small effects of acetate, propionate and butyrate we observed here may not be physiologically relevant, but the effects of CFMB and Compound 4 on somatostatin secretion suggest that it may be possible to manipulate pancreatic secretion pharmacologically with agonists of the FFAR2 and 3 receptors, a finding which deserves further investigation.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"11 1","pages":"103 - 111"},"PeriodicalIF":2.2,"publicationDate":"2019-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2019.1587976","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41636984","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: 20
Gene expression patterns in synchronized islet populations. 同步胰岛群体的基因表达模式。
IF 2.2 4区 医学
Islets Pub Date : 2019-01-01 Epub Date: 2019-05-03 DOI: 10.1080/19382014.2019.1581544
Nikita Mukhitov, Joel E Adablah, Michael G Roper
{"title":"Gene expression patterns in synchronized islet populations.","authors":"Nikita Mukhitov,&nbsp;Joel E Adablah,&nbsp;Michael G Roper","doi":"10.1080/19382014.2019.1581544","DOIUrl":"https://doi.org/10.1080/19382014.2019.1581544","url":null,"abstract":"<p><p>In vivo levels of insulin are oscillatory with a period of ~5-10 minutes, indicating that the islets of Langerhans within the pancreas are synchronized. While the synchronizing factors are still under investigation, one result of this behavior is expected to be coordinated and oscillatory intracellular factors, such as intracellular Ca<sup>2+</sup> levels, throughout the islet population. In other cell types, oscillatory intracellular signals, like intracellular Ca<sup>2+</sup>, have been shown to affect specific gene expression. To test how the gene expression landscape may differ between a synchronized islet population with its reproducible intracellular oscillations and an unsynchronized islet population with heterogeneous oscillations, gene set enrichment analysis (GSEA) was used to compare an islet population that had been synchronized using a glucose wave with a 5-min period, and an unsynchronized islet population. In the population exposed to the glucose wave, 58/62 islets showed synchronization as evidenced by coordinated intracellular Ca<sup>2+</sup> oscillations with an average oscillation period of 5.1 min, while in the unsynchronized population 29/62 islets showed slow oscillations with an average period of 5.2 min. The synchronized islets also had a significantly smaller drift of their oscillation period during the experiment as compared to the unsynchronized population. GSEA indicated that the synchronized population had reduced expression of gene sets related to protein translation, protein turnover, energy expenditure, and insulin synthesis, while those that were related to maintenance of cell morphology were increased.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"11 2","pages":"21-32"},"PeriodicalIF":2.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2019.1581544","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37210220","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
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