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, Keiko Omori, Chris Orr, Jeffrey Rawson, Donald C Dafoe, Ismail H Al-Abdullah, Fouad Kandeel, Yoko Mullen","doi":"10.1080/19382014.2019.1696127","DOIUrl":"https://doi.org/10.1080/19382014.2019.1696127","url":null,"abstract":"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 IL6 expression in pancreatic tissue correlated negatively with post-isolation islet yield. Islets isolated from donors highly expressing IFNG in PBMCs and MAC1 in pancreatic tissue functioned poorly in vivo when transplanted in diabetic NODscid mice. Furthermore, the increased MAC1 in pancreatic tissue was positively correlated with donor hospitalization time. Brain death duration positively correlated with higher expression of IL1B in PBMCs and TNF in both PBMCs and pancreatic tissue but failed to show a significant correlation with islet yield and in vivo function. The study indicates that the increased inflammatory genes in donor pancreatic tissues may be considered as biomarkers associated with poor islet isolation outcome.","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, 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

RORB and RORC associate with human islet dysfunction and inhibit insulin secretion in INS-1 cells. RORB和RORC与胰岛功能障碍有关，并抑制INS-1细胞的胰岛素分泌。

IF 2.2 4区医学

Islets Pub Date : 2019-01-01 Epub Date: 2019-02-14 DOI: 10.1080/19382014.2019.1566684

Jalal Taneera, Abdul Khader Mohammed, Sarah Dhaiban, Mawieh Hamad, Rashmi B Prasad, Nabil Sulaiman, Albert Salehi

{"title":"RORB and RORC associate with human islet dysfunction and inhibit insulin secretion in INS-1 cells.","authors":"Jalal Taneera, Abdul Khader Mohammed, Sarah Dhaiban, Mawieh Hamad, Rashmi B Prasad, Nabil Sulaiman, Albert Salehi","doi":"10.1080/19382014.2019.1566684","DOIUrl":"https://doi.org/10.1080/19382014.2019.1566684","url":null,"abstract":"Little is known about the expression and function of Retinoic acid-related orphan receptors (RORA, B, and C) in pancreatic β cells. Here in, we utilized cDNA microarray and RNA sequencing approaches to investigate the expression pattern of ROR receptors in normal and diabetic human pancreatic islets. Possible correlations between RORs expression and HbA1c levels as well as insulin secretory capacity in isolated human islets were evaluated. The impact of RORB and RORC expression on insulin secretion in INS-1 (832/13) cells was validated as well. While RORA was the highest expressed gene among the three RORs in human islet cells, RORC was the highest expressed in INS-1 cells (832/13) and while RORB was the lowest expressed gene in human islet cells, RORA was the highest expressed in INS-1 cells (832/13). The expression of RORB and RORC was significantly lower in diabetic/hyperglycemic donors as compared with non-diabetic counterparts. Furthermore, while the expression of RORB correlated positively with insulin secretion and negatively with HbA1c, that of RORC correlated negatively with HbA1c. The expression pattern of RORA did not correlate with either of the two parameters. siRNA silencing of RORB or RORC in INS-1 (832/13) cells resulted in a significant downregulation of insulin mRNA expression and insulin secretion. These findings suggest that RORB and RORC are part of the molecular cascade that regulates insulin secretion in pancreatic β cells; and insight that provides for further work on the potential therapeutic utility of RORB and RORC genes in β cell dysfunction in type 2 diabetes.","PeriodicalId":14671,"journal":{"name":"Islets","volume":" ","pages":"10-20"},"PeriodicalIF":2.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2019.1566684","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40448338","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: 16

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