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, Joel E Adablah, Michael G Roper","doi":"10.1080/19382014.2019.1581544","DOIUrl":"https://doi.org/10.1080/19382014.2019.1581544","url":null,"abstract":"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 Ca2+ levels, throughout the islet population. In other cell types, oscillatory intracellular signals, like intracellular Ca2+, 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 Ca2+ 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.","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

Glutamate decarboxylase 67 contributes to compensatory insulin secretion in aged pancreatic islets. 谷氨酸脱羧酶67参与老年胰岛代偿性胰岛素分泌。

IF 2.2 4区医学

Islets Pub Date : 2019-01-01 Epub Date: 2019-05-14 DOI: 10.1080/19382014.2019.1599708

Jung Hoon Cho, Kyeong-Min Lee, Yun-Il Lee, Hong Gil Nam, Won Bae Jeon

{"title":"Glutamate decarboxylase 67 contributes to compensatory insulin secretion in aged pancreatic islets.","authors":"Jung Hoon Cho, Kyeong-Min Lee, Yun-Il Lee, Hong Gil Nam, Won Bae Jeon","doi":"10.1080/19382014.2019.1599708","DOIUrl":"https://doi.org/10.1080/19382014.2019.1599708","url":null,"abstract":"Pancreatic islets play an essential role in regulating blood glucose levels. Age-dependent development of glucose intolerance and insulin resistance results in hyperglycemia, which in turn stimulates insulin synthesis and secretion from aged islets, to fulfill the increased demand for insulin. However, the mechanism underlying enhanced insulin secretion remains unknown. Glutamic acid decarboxylase 67 (GAD67) catalyzes the conversion of glutamate into γ-aminobutyric acid (GABA) and CO2. Both glutamate and GABA can affect islet function. Here, we investigated the role of GAD67 in insulin secretion in young (3 month old) and aged (24 month old) C57BL/6J male mice. Unlike young mice, aged mice displayed glucose-intolerance and insulin-resistance. However, aged mice secreted more insulin and showed lower fed blood glucose levels than young mice. GAD67 levels in primary islets increased with aging and in response to high glucose levels. Inhibition of GAD67 activity using a potent inhibitor of GAD, 3-mercaptopropionic acid, abrogated glucose-stimulated insulin secretion from a pancreatic β-cell line and from young and aged islets. Collectively, our results suggest that blood glucose levels regulate GAD67 expression, which contributes to β-cell responses to impaired glucose homeostasis caused by advanced aging.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"11 2","pages":"33-43"},"PeriodicalIF":2.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2019.1599708","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37234662","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: 7

Use of anti-inflammatory agents in clinical islet cell transplants: A qualitative systematic analysis. 抗炎药在临床胰岛细胞移植中的应用:定性系统分析。

IF 2.2 4区医学

Islets Pub Date : 2019-01-01 DOI: 10.1080/19382014.2019.1601543

Kristen R Szempruch, Oyshik Banerjee, Rebecca C McCall, Chirag S Desai

引用次数: 22

Palmitate is not an effective fuel for pancreatic islets and amplifies insulin secretion independent of calcium release from endoplasmic reticulum. 棕榈酸酯不是胰岛的有效燃料，它能增加独立于内质网钙释放的胰岛素分泌。

IF 2.2 4区医学

Islets Pub Date : 2019-01-01 Epub Date: 2019-05-14 DOI: 10.1080/19382014.2019.1601490

Iok Teng Kuok, Austin M Rountree, Seung-Ryoung Jung, Ian R Sweet

{"title":"Palmitate is not an effective fuel for pancreatic islets and amplifies insulin secretion independent of calcium release from endoplasmic reticulum.","authors":"Iok Teng Kuok, Austin M Rountree, Seung-Ryoung Jung, Ian R Sweet","doi":"10.1080/19382014.2019.1601490","DOIUrl":"https://doi.org/10.1080/19382014.2019.1601490","url":null,"abstract":"The aim of the study was to determine the acute contribution of fuel oxidation in mediating the increase in insulin secretion rate (ISR) in response to fatty acids. Measures of mitochondrial metabolism, as reflected by oxygen consumption rate (OCR) and cytochrome c reduction, calcium signaling, and ISR by rat islets were used to evaluate processes stimulated by acute exposure to palmitic acid (PA). The contribution of mitochondrial oxidation of PA was determined in the presence and absence of a blocker of mitochondrial transport of fatty acids (etomoxir) at different glucose concentrations. Subsequent to increasing glucose from 3 to 20 mM, PA caused small increases in OCR and cytosolic calcium (about 20% of the effect of glucose). In contrast, the effect of PA on ISR was almost 3 times that by glucose, suggesting that the metabolism of PA is not the dominant mechanism mediating PA's effect on ISR. This was further supported by lack of inhibition of PA-stimulated OCR and ISR when blocking entry of PA into mitochondria (with etomoxir), and PA's lack of stimulation of reduced cytochrome c in the presence of high glucose. Consistent with the lack of metabolic stimulation by PA, an inhibitor of calcium release from the endoplasmic reticulum, but not a blocker of L-type calcium channels, abolished the PA-induced elevation of cytosolic calcium. Notably, ISR was unaffected by thapsigargin showing the dissociation of endoplasmic reticulum calcium release and second phase insulin secretion. In conclusion, stimulation of ISR by PA was mediated by mechanisms largely independent of the oxidation of the fuel.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"11 3","pages":"51-64"},"PeriodicalIF":2.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2019.1601490","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37234660","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: 9

Pancreatic beta cell/islet mass and body mass index. 胰腺细胞/胰岛质量和身体质量指数。

IF 2.2 4区医学

Islets Pub Date : 2019-01-01 Epub Date: 2019-01-22 DOI: 10.1080/19382014.2018.1557486

Michael P Dybala, Scott K Olehnik, Jonas L Fowler, Karolina Golab, J Michael Millis, Justyna Golebiewska, Piotr Bachul, Piotr Witkowski, Manami Hara

{"title":"Pancreatic beta cell/islet mass and body mass index.","authors":"Michael P Dybala, Scott K Olehnik, Jonas L Fowler, Karolina Golab, J Michael Millis, Justyna Golebiewska, Piotr Bachul, Piotr Witkowski, Manami Hara","doi":"10.1080/19382014.2018.1557486","DOIUrl":"https://doi.org/10.1080/19382014.2018.1557486","url":null,"abstract":"Body mass index (BMI) is widely used to define obesity. In studies of pancreatic beta-cell/islet mass, BMI is also a common standard for matching control subjects in comparative studies along with age and sex, based on the existing dogma of their significant positive correlation reported in the literature. We aimed to test the feasibility of BMI and BSA to assess obesity and predict beta-cell/islet mass. We used National Health and Nutrition Examination Survey (NHANES) data that provided dual-energy Xray absorptiometry (DXA)-measured fat mass (percent body fat; %BF), BMI, and BSA for adult subjects (20-75y; 4,879 males and 4,953 females). We then analyzed 152 cases of islet isolation performed at our center for correlation between islet yields and various donor anthropometric indices. From NHANES, over 50% of male subjects and 60% of female subjects with BMI:20.1-28.1 were obese as defined by %BF, indicating a poor correlation between BMI and %BF. BSA was also a poor indicator of %BF, as broad overlap was observed in different BSA ranges. Additionally, BMI and BSA ranges markedly varied between sex and race/ethnicity groups. From islet isolation, BMI and BSA accounted for only a small proportion of variance in islet equivalent (IEQ; r2 = 0.09 and 0.11, respectively). BMI and obesity were strongly correlated in cases of high BMI subjects. However, the critical populations were non-obese subjects with BMI ranging from 20.1-28.1, in which a substantial proportion of individuals may carry excess body fat. Correlations between BMI, BSA, pancreas weight and beta-cell/islet mass were low.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"11 1","pages":"1-9"},"PeriodicalIF":2.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2018.1557486","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36884784","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: 12

Characterization of host defense molecules in the human pancreas. 人类胰腺中宿主防御分子的特征。

IF 1.9 4区医学

Islets Pub Date : 2019-01-01 Epub Date: 2019-06-26 DOI: 10.1080/19382014.2019.1585165

Anton Stenwall, Sofie Ingvast, Oskar Skog, Olle Korsgren

{"title":"Characterization of host defense molecules in the human pancreas.","authors":"Anton Stenwall, Sofie Ingvast, Oskar Skog, Olle Korsgren","doi":"10.1080/19382014.2019.1585165","DOIUrl":"10.1080/19382014.2019.1585165","url":null,"abstract":"The gut microbiota can play a role in pancreatitis and, likely, in the development of type 1 diabetes (T1D). Anti-microbial peptides and secretory proteins are important mediators of the innate immune response against bacteria but their expression in the human pancreas is not fully known. In this study, immunohistochemistry was used to analyze the expression of seven anti-microbial peptides (Defensin α1, α4, β1-4 and Cathelicidin) and two secretory proteins with known antimicrobial properties (REG3A and GP2) in pancreatic and duodenal biopsies from 10 non-diabetic organ donors and one organ donor that died at onset of T1D. Immunohistochemical data was compared with previously published whole-transcriptome data sets. Seven (Defensin α1, β2, β3, α4, GP2, Cathelicidin, and REG3A) host defense molecules showed positive staining patterns in most non-diabetic organ donors, whereas two (Defensin β1 and β4) were negative in all non-diabetic donors. Two molecules (Defensin α1 and GP2) were restricted to the exocrine pancreas whereas two (Defensin β3, α4) were only expressed in islet tissue. Cathelicidin, β2, and REG3A were expressed in both islets and exocrine tissue. The donor that died at onset of T1D had generally less positivity for the host defense molecules, but, notably, this pancreas was the only one where defensin β1 was found. Neither donor age, immune-cell infiltration, nor duodenal expression correlated to the pancreatic expression of host defense molecules. In conclusion, these findings could have important implications for the inflammatory processes in diabetes and pancreatitis as we find several host defense molecules expressed by the pancreatic tissue.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"11 4","pages":"89-101"},"PeriodicalIF":1.9,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/d0/kisl-11-04-1585165.PMC6682263.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37367359","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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