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EndoC-βH1 cells display increased sensitivity to sodium palmitate when cultured in DMEM/F12 medium. EndoC-βH1细胞在DMEM/F12培养基中培养时,对棕榈酸钠的敏感性增加。
IF 2.2 4区 医学
Islets Pub Date : 2017-05-04 Epub Date: 2017-02-28 DOI: 10.1080/19382014.2017.1296995
Camilla Krizhanovskii, Hjalti Kristinsson, Andris Elksnis, Xuan Wang, Hamid Gavali, Peter Bergsten, Raphael Scharfmann, Nils Welsh
{"title":"EndoC-βH1 cells display increased sensitivity to sodium palmitate when cultured in DMEM/F12 medium.","authors":"Camilla Krizhanovskii,&nbsp;Hjalti Kristinsson,&nbsp;Andris Elksnis,&nbsp;Xuan Wang,&nbsp;Hamid Gavali,&nbsp;Peter Bergsten,&nbsp;Raphael Scharfmann,&nbsp;Nils Welsh","doi":"10.1080/19382014.2017.1296995","DOIUrl":"https://doi.org/10.1080/19382014.2017.1296995","url":null,"abstract":"<p><p>Aims - Human pancreatic islets are known to die in response to the free fatty acid of sodium palmitate when cultured in vitro. This is in contrast to EndoC-βH1 cells, which in our hands are not sensitive to the cell death-inducing effects sodium palmitate, making these cells seemingly unsuitable for lipotoxicity studies. However, the EndoC-βH1 cells are routinely cultured in a nutrient mixture based on Dulbecco's Modified Eagle Medium (DMEM), which may not be the optimal choice for studies dealing with lipotoxicity. The aim of the present investigation was to define culture conditions that render EndoC-βH1 cells sensitive to toxic effects of sodium palmitate. Methods - EndoC-βH1 cells were cultured at standard conditions in either DMEM or DMEM/F12 culture medium. Cell death was analyzed using propidium iodide staining and flow cytometry. Insulin release and content was quantified using a human insulin ELISA. Results - We presently observe that substitution of DMEM for a DMEM/Ham's F12 mixture (50%/50% vol/vol) renders the cells sensitive to the apoptotic effects of sodium palmitate and sodium palmitate + high glucose leading to an increased cell death. Supplementation of the DMEM culture medium with linoleic acid partially mimicked the effect of DMEM/F12. Culture of EndoC-βH1 cells in DMEM/F12 resulted also in increased proliferation, ROS production and insulin contents, but markers for metabolic stress, autophagy or amyloid deposits were unaffected. Conclusions - The culture conditions for EndoC-βH1 cells can be modified so these cells display signs of lipotoxicity in response to sodium palmitate.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"9 3","pages":"e1296995"},"PeriodicalIF":2.2,"publicationDate":"2017-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2017.1296995","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34798804","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: 22
Effect of co-culture of mesenchymal stem/stromal cells with pancreatic islets on viability and function outcomes: a systematic review and meta-analysis. 间充质干细胞/基质细胞与胰岛共培养对生存能力和功能结果的影响:系统综述和荟萃分析
IF 2.2 4区 医学
Islets Pub Date : 2017-03-04 DOI: 10.1080/19382014.2017.1286434
Bianca Marmontel de Souza, Ana Paula Bouças, Fernanda Dos Santos de Oliveira, Karina Pires Reis, Patrícia Ziegelmann, Andrea Carla Bauer, Daisy Crispim
{"title":"Effect of co-culture of mesenchymal stem/stromal cells with pancreatic islets on viability and function outcomes: a systematic review and meta-analysis.","authors":"Bianca Marmontel de Souza, Ana Paula Bouças, Fernanda Dos Santos de Oliveira, Karina Pires Reis, Patrícia Ziegelmann, Andrea Carla Bauer, Daisy Crispim","doi":"10.1080/19382014.2017.1286434","DOIUrl":"10.1080/19382014.2017.1286434","url":null,"abstract":"<p><p>The maintenance of viable and functional pancreatic islets is crucial for successful islet transplantation from brain-dead donors. To overcome islet quality loss during culture, some studies have co-cultured islets with mesenchymal stem/stromal cells (MSC). However, it is still uncertain if MSC-secreted factors are enough to improve islet quality or if a physical contact between MSCs and islets is needed. Therefore, we performed a systematic review and meta-analysis to clarify the effect of different culture contact systems of islets with MSCs on viability and insulin secretion outcomes. Pubmed and Embase were searched. Twenty studies fulfilled the eligibility criteria and were included in the qualitative synthesis and/or meta-analysis. For both outcomes, pooled weighted mean differences (WMD) between islet cultured alone (control group) and the co-culture condition were calculated. Viability mean was higher in islets co-cultured with MSCs compared with islet cultured alone [WMD = 18.08 (95% CI 12.59-23.57)]. The improvement in viability was higher in islets co-cultured in indirect or mixed contact with MSCs than in direct physical contact (P <0.001). Moreover, the mean of insulin stimulation index (ISI) was higher in islets from co-culture condition compared with islet cultured alone [WMD = 0.83 (95% CI 0.54-1.13)], independently of contact system. Results from the studies that were analyzed only qualitatively are in accordance with meta-analysis data. Co-culture of islets with MSCs has the potential for protecting islets from injury during culture period. Moreover, culture time appears to influence the beneficial effect of different methods of co-culture on viability and function of islets.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"9 1","pages":"30-42"},"PeriodicalIF":2.2,"publicationDate":"2017-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2017.1286434","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46974338","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: 42
Evidence of stress in β cells obtained with laser capture microdissection from pancreases of brain dead donors. 激光捕获显微解剖获得脑死亡供体胰腺β细胞应激的证据。
IF 2.2 4区 医学
Islets Pub Date : 2017-03-04 DOI: 10.1080/19382014.2017.1283083
Aref Ebrahimi, Min-Ho Jung, Jonathan M Dreyfuss, Hui Pan, Dennis Sgroi, Susan Bonner-Weir, Gordon C Weir
{"title":"Evidence of stress in β cells obtained with laser capture microdissection from pancreases of brain dead donors.","authors":"Aref Ebrahimi,&nbsp;Min-Ho Jung,&nbsp;Jonathan M Dreyfuss,&nbsp;Hui Pan,&nbsp;Dennis Sgroi,&nbsp;Susan Bonner-Weir,&nbsp;Gordon C Weir","doi":"10.1080/19382014.2017.1283083","DOIUrl":"https://doi.org/10.1080/19382014.2017.1283083","url":null,"abstract":"<p><p>Isolated islets used for transplantation are known to be stressed, which can result from the circumstances of death, in particular brain death, the preservation of the pancreas with its warm and cold ischemia, from the trauma of the isolation process, and the complex events that occur during tissue culture. The current study focused upon the events that occur before the islet isolation procedure. Pancreases were obtained from brain dead donors (n = 7) with mean age 50 (11) and normal pancreatic tissue obtained at surgery done for pancreatic neoplasms (n = 7), mean age 69 (9). Frozen sections were subjected to laser capture microdissection (LCM) to obtain β-cell rich islet tissue, from which extracted RNA was analyzed with microarrays. Gene expression of the 2 groups was evaluated with differential expression analysis for genes and pathways. Marked changes were found in pathways concerned with endoplasmic reticulum stress with its unfolded protein response (UPR), apoptotic pathways and components of inflammation. In addition, there were changes in genes important for islet cell identity. These findings advance our understanding of why islets are stressed before transplantation, which may lead to strategies to reduce this stress and lead to better clinical outcomes.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"9 2","pages":"19-29"},"PeriodicalIF":2.2,"publicationDate":"2017-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2017.1283083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34776966","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: 15
Inhibition of voltage-dependent potassium channels mediates cAMP-potentiated insulin secretion in rat pancreatic β cells 电压依赖性钾通道的抑制介导cAMP增强的大鼠胰腺β细胞胰岛素分泌
IF 2.2 4区 医学
Islets Pub Date : 2017-02-15 DOI: 10.1080/19382014.2017.1280644
Yunfeng Liu, Xiangqin Zhong, Yaqin Ding, Lele Ren, T. Bai, Mengmeng Liu, Zhihong Liu, Yangyan Guo, Qing Guo, Yu Zhang, Jing Yang, Yi Zhang
{"title":"Inhibition of voltage-dependent potassium channels mediates cAMP-potentiated insulin secretion in rat pancreatic β cells","authors":"Yunfeng Liu, Xiangqin Zhong, Yaqin Ding, Lele Ren, T. Bai, Mengmeng Liu, Zhihong Liu, Yangyan Guo, Qing Guo, Yu Zhang, Jing Yang, Yi Zhang","doi":"10.1080/19382014.2017.1280644","DOIUrl":"https://doi.org/10.1080/19382014.2017.1280644","url":null,"abstract":"ABSTRACT Insulin secretion is essential for maintenance of glucose homeostasis. An important intracellular signal regulating insulin secretion is cAMP. In this report, we showed that an increase of cAMP induced by adenylyl cyclase (AC) activator forskolin or by cAMP analog db-cAMP not only potentiated insulin secretion but also inhibited Kv channels, and these effects were reversed by AC inhibitor SQ22536. The cAMP-mediated Kv channel inhibition resulted in prolongation of action potential duration, which partly accounts for the elevation of intracellular Ca2+ induced by activation of cAMP signaling. Taken together, the results suggest that Kv channels are involved in cAMP-potentiated insulin secretion in pancreatic β cells.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"9 1","pages":"11 - 18"},"PeriodicalIF":2.2,"publicationDate":"2017-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2017.1280644","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45168293","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: 6
Effect of moderate and high intensity chronic exercise on the pancreatic islet morphometry in healthy rats: BDNF receptor participation 中、高强度慢性运动对健康大鼠胰岛形态的影响:BDNF受体的参与
IF 2.2 4区 医学
Islets Pub Date : 2017-01-02 DOI: 10.1080/19382014.2016.1260796
A. Jiménez-Maldonado, Adolfo Virgen-Ortiz, V. Melnikov, Alejandrina Rodríguez-Hernández, A. Gamboa-Domínguez, S. Montero, Jesús Muñiz-Murguía, M. Lemus, E. Roces de Álvarez-Buylla
{"title":"Effect of moderate and high intensity chronic exercise on the pancreatic islet morphometry in healthy rats: BDNF receptor participation","authors":"A. Jiménez-Maldonado, Adolfo Virgen-Ortiz, V. Melnikov, Alejandrina Rodríguez-Hernández, A. Gamboa-Domínguez, S. Montero, Jesús Muñiz-Murguía, M. Lemus, E. Roces de Álvarez-Buylla","doi":"10.1080/19382014.2016.1260796","DOIUrl":"https://doi.org/10.1080/19382014.2016.1260796","url":null,"abstract":"ABSTRACT The function and morphology of β-cells is largely dependent on insulin demand. As β-cells cover a bigger cell proportion in pancreas islets, changes of insulin producer cells affect the whole pancreatic islet morphology. Growth factors as the neurotrophins regulate the pancreas physiology, besides; physical exercise increases insulin sensitivity, and further modifies brain derived neurotrophic factor (BDNF) concentration in plasma. The aim of this study was to investigate the effects of chronic exercise (running in a treadmill for 8 weeks) intensity on pancreatic islet morphometry in healthy state. The BDNF receptor effect on the pancreatic islet morphometry was also evaluated. Adult male Wistar rats were divided in 6 groups: Control (C); moderate intensity training (MIT); high intensity training (HIT) did not treat with BDNF receptor inhibitor (K252a), and C, MIT and HIT treated with K252a. The results shown that chronic exercise induces β-cells hypertrophy without BDNF receptor participation. On the other hand, the moderate exercise increases the number of β cells per islet; the last effect does not require TrkB participation. In sedentary conditions, the K252a treatment reduced the β-cell density. Exercise intensity has differential effects on pancreas islet morphometry in healthy model; furthermore, BDNF receptor plays a role to maintain the amount of β-cells in sedentary state.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"9 1","pages":"1 - 10"},"PeriodicalIF":2.2,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2016.1260796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41772957","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
Long-term function and optimization of mouse and human islet transplantation in the subcutaneous device-less site 小鼠和人胰岛在皮下无装置部位移植的长期功能和优化
IF 2.2 4区 医学
Islets Pub Date : 2016-11-01 DOI: 10.1080/19382014.2016.1253652
A. Pepper, A. Bruni, R. Pawlick, B. Gala-Lopez, Y. Rafiei, John Wink, T. Kin, A. M. J. Shapiro
{"title":"Long-term function and optimization of mouse and human islet transplantation in the subcutaneous device-less site","authors":"A. Pepper, A. Bruni, R. Pawlick, B. Gala-Lopez, Y. Rafiei, John Wink, T. Kin, A. M. J. Shapiro","doi":"10.1080/19382014.2016.1253652","DOIUrl":"https://doi.org/10.1080/19382014.2016.1253652","url":null,"abstract":"ABSTRACT Clinical islet transplantation has routinely been demonstrated to be an efficacious means of restoring glycemic control in select patients with autoimmune diabetes. Notwithstanding marked progress and improvements, the broad-spectrum application of this treatment option is restricted by the complications associated with intrahepatic portal cellular infusion and the scarcity of human donor pancreata. Recent progress in stem cell biology has demonstrated that the potential to expand new β cells for clinical transplantation is now a reality. As such, research focus is being directed toward optimizing safe extrahepatic transplant sites to house future alternative β cell sources for clinical use. The present study expands on our previous development of a prevascularized subcutaneous device-less (DL) technique for cellular transplantation, by demonstrating long-term (>365 d) durable syngeneic murine islet graft function. Furthermore, histological analysis of tissue specimens collected immediately post-DL site creation and acutely post-human islet transplantation demonstrates that this technique results in close apposition of the neovascularized collagen to the transplanted cells without dead space, thereby avoiding hypoxic luminal dead-space. Murine islets transplanted into the DL site created by a larger luminal diameter (6-Fr.) (n = 11), reversed diabetes to the similar capacity as our standard DL method (5-Fr.)(n = 9). Furthermore, glucose tolerance testing did not differ between these 2 transplant groups (p > 0 .05). Taken together, this further refinement of the DL transplant approach facilitates a simplistic means of islet infusion, increases the transplant volume capacity and may provide an effective microenvironment to house future alternative β cell sources.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"8 1","pages":"186 - 194"},"PeriodicalIF":2.2,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2016.1253652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59985351","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: 22
Serine racemase is expressed in islets and contributes to the regulation of glucose homeostasis 丝氨酸消旋酶在胰岛中表达,参与调节葡萄糖稳态
IF 2.2 4区 医学
Islets Pub Date : 2016-11-01 DOI: 10.1080/19382014.2016.1260797
A. Lockridge, Daniel Baumann, Brian Akhaphong, Alleah Abrenica, Robert F. Miller, E. Alejandro
{"title":"Serine racemase is expressed in islets and contributes to the regulation of glucose homeostasis","authors":"A. Lockridge, Daniel Baumann, Brian Akhaphong, Alleah Abrenica, Robert F. Miller, E. Alejandro","doi":"10.1080/19382014.2016.1260797","DOIUrl":"https://doi.org/10.1080/19382014.2016.1260797","url":null,"abstract":"ABSTRACT NMDA receptors (NMDARs) have recently been discovered as functional regulators of pancreatic β-cell insulin secretion. While these excitatory receptor channels have been extensively studied in the brain for their role in synaptic plasticity and development, little is known about how they work in β-cells. In neuronal cells, NMDAR activation requires the simultaneous binding of glutamate and a rate-limiting co-agonist, such as D-serine. D-serine levels and availability in most of the brain rely on endogenous synthesis by the enzyme serine racemase (Srr). Srr transcripts have been reported in human and mouse islets but it is not clear whether Srr is functionally expressed in β-cells or what its role in the pancreas might be. In this investigation, we reveal that Srr protein is highly expressed in primary human and mouse β-cells. Mice with whole body deletion of Srr (Srr KO) show improved glucose tolerance through enhanced insulin secretory capacity, possibly through Srr-mediated alterations in islet NMDAR expression and function. We observed elevated insulin sensitivity in some animals, suggesting Srr metabolic regulation in other peripheral organs as well. Srr expression in neonatal and embryonic islets, and adult deficits in Srr KO pancreas weight and islet insulin content, point toward a potential role for Srr in pancreatic development. These data reveal the first evidence that Srr may regulate glucose homeostasis in peripheral tissues and provide circumstantial evidence that D-serine may be an endogenous islet NMDAR co-agonist in β-cells.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"8 1","pages":"195 - 206"},"PeriodicalIF":2.2,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2016.1260797","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59985399","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: 26
Resistin is produced by rat pancreatic islets and regulates insulin and glucagon in vitro secretion 抵抗素是由大鼠胰岛产生的,在体外调节胰岛素和胰高血糖素的分泌
IF 2.2 4区 医学
Islets Pub Date : 2016-10-31 DOI: 10.1080/19382014.2016.1251538
M. Sassek, E. Pruszyńska‐Oszmałek, P. Kołodziejski, D. Szczepankiewicz, P. Kaczmarek, M. Wieloch, Katarzyna Kurto, L. Nogowski, K. Nowak, M. Strowski, P. Maćkowiak
{"title":"Resistin is produced by rat pancreatic islets and regulates insulin and glucagon in vitro secretion","authors":"M. Sassek, E. Pruszyńska‐Oszmałek, P. Kołodziejski, D. Szczepankiewicz, P. Kaczmarek, M. Wieloch, Katarzyna Kurto, L. Nogowski, K. Nowak, M. Strowski, P. Maćkowiak","doi":"10.1080/19382014.2016.1251538","DOIUrl":"https://doi.org/10.1080/19382014.2016.1251538","url":null,"abstract":"ABSTRACT Resistin participates in the regulation of energy homeostasis, insulin resistance, and inflammation. The potential expression in pancreas, and modulation of the endocrine pancreas secretion by resistin is not well characterized, therefore, we examined it on several levels. We examined the localization of resistin in rat pancreatic islets by immunohistochemistry and immunofluorescence, and the potential presence of resistin mRNA by RT-PCR and protein by Western Blot in these structures. In addition, we studied the regulation of insulin and glucagon secretion by resistin in pancreatic INS-1E β- and InR-G9 α-cell lines as well as isolated rat pancreatic islets. We identified resistin immunoreactivity in the periphery of rat pancreatic islets and confirmed the expression of resistin at mRNA and protein level. Obtained data indicated that resistin is co-localized with glucagon in pancreatic α-cells. In addition, we found that in vitro resistin decreased insulin secretion from INS-1E cells and pancreatic islets at normal (6 mM) and high (24 mM) glucose concentrations, and also decreased glucagon secretion from G9 cells and pancreatic islets at 1 mM, whereas a stimulation of glucagon secretion was observed at 6 mM glucose. Our results suggest that resistin can modulate the secretion of insulin and glucagon from clonal β or α cells, and from pancreatic islets.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"8 1","pages":"177 - 185"},"PeriodicalIF":2.2,"publicationDate":"2016-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2016.1251538","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59985422","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: 8
Culture at low glucose up-regulates mitochondrial function in pancreatic β cells with accompanying effects on viability 低糖培养可上调胰腺β细胞线粒体功能,并对细胞活力产生影响
IF 2.2 4区 医学
Islets Pub Date : 2016-10-20 DOI: 10.1080/19382014.2016.1246637
I. Hals, Rinku Singh, Zuheng Ma, H. Scholz, A. Björklund, V. Grill
{"title":"Culture at low glucose up-regulates mitochondrial function in pancreatic β cells with accompanying effects on viability","authors":"I. Hals, Rinku Singh, Zuheng Ma, H. Scholz, A. Björklund, V. Grill","doi":"10.1080/19382014.2016.1246637","DOIUrl":"https://doi.org/10.1080/19382014.2016.1246637","url":null,"abstract":"ABSTRACT We tested whether exposure of β cells at reduced glucose leads to mitochondrial adaptions and whether such adaptions modulate effects of hypoxia. Rat islets, human islets and INS-1 832/13 cells were pre-cultured short term at half standard glucose concentrations (5.5 mM for rat islets and cells, 2.75 mM for human islets) without overtly negative effects on subsequently measured function (insulin secretion and cellular insulin contents) or on viability. Culture at half standard glucose upregulated complex I and tended to upregulate complex II in islets and INS-1 cells alike. An increased release of lactate dehydrogenase that followed exposure to hypoxia was attenuated in rat islets which had been pre-cultured at half standard glucose. In INS-1 cells exposure to half standard glucose attenuated hypoxia-induced effects on several viability parameters (MTT, cell number and incremental apoptotic DNA). Thus culture at reduced glucose of pancreatic islets and clonal β cells leads to mitochondrial adaptions which possibly lessen the negative impact of hypoxia on β cell viability. These findings appear relevant in the search for optimization of pre-transplant conditions in a clinical setting.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"8 1","pages":"165 - 176"},"PeriodicalIF":2.2,"publicationDate":"2016-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2016.1246637","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59985261","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: 3
The P21-activated kinase PAK4 is implicated in fatty-acid potentiation of insulin secretion downstream of free fatty acid receptor 1 p21活化的激酶PAK4参与游离脂肪酸受体1下游胰岛素分泌的脂肪酸增强
IF 2.2 4区 医学
Islets Pub Date : 2016-10-04 DOI: 10.1080/19382014.2016.1243191
Valérie Bergeron, J. Ghislain, V. Poitout
{"title":"The P21-activated kinase PAK4 is implicated in fatty-acid potentiation of insulin secretion downstream of free fatty acid receptor 1","authors":"Valérie Bergeron, J. Ghislain, V. Poitout","doi":"10.1080/19382014.2016.1243191","DOIUrl":"https://doi.org/10.1080/19382014.2016.1243191","url":null,"abstract":"ABSTRACT Free fatty acid receptor 1 (FFA1/GPR40) plays a key role in the potentiation of glucose-stimulated insulin secretion by fatty acids in pancreatic β cells. We previously demonstrated that GPR40 signaling leads to cortical actin remodeling and potentiates the second phase of insulin secretion. In this study, we examined the role of p21 activated kinase 4 (PAK4), a known regulator of cytoskeletal dynamics, in GPR40-dependent potentiation of insulin secretion. The fatty acid oleate induced PAK4 phosphorylation in human islets, in isolated mouse islets and in the insulin secreting cell line INS832/13. However, oleate-induced PAK4 phosphorylation was not observed in GPR40-null mouse islets. siRNA-mediated knockdown of PAK4 in INS832/13 cells abrogated the potentiation of insulin secretion by oleate, whereas PAK7 knockdown had no effect. Our results indicate that PAK4 plays an important role in the potentiation of insulin secretion by fatty acids downstream of GPR40.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"8 1","pages":"157 - 164"},"PeriodicalIF":2.2,"publicationDate":"2016-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19382014.2016.1243191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59985195","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: 7
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