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Camilla Krizhanovskii, Hjalti Kristinsson, Andris Elksnis, Xuan Wang, Hamid Gavali, Peter Bergsten, Raphael Scharfmann, Nils Welsh
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...
February 28, 2017: Islets
Aref Ebrahimi, Min-Ho Jung, Jonathan M Dreyfuss, Hui Pan, Dennis Sgroi, Susan Bonner-Weir, Gordon C Weir
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)...
March 4, 2017: Islets
Bianca Marmontel de Souza, Ana Paula Bouças, Fernanda Dos Santos de Oliveira, Karina Pires Reis, Patrícia Ziegelmann, Andrea Carla Bauer, Daisy Crispim
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...
March 4, 2017: Islets
Yunfeng Liu, Xiangqin Zhong, Yaqin Ding, Lele Ren, Tao Bai, Mengmeng Liu, Zhihong Liu, Yangyan Guo, Qing Guo, Yu Zhang, Jing Yang, Yi Zhang
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 Ca(2+) induced by activation of cAMP signaling...
March 4, 2017: Islets
Alberto Jiménez-Maldonado, Adolfo Virgen-Ortiz, Valery Melnikov, Alejandrina Rodríguez-Hernández, Armando Gamboa-Domínguez, Sergio Montero, Jesús Muñiz-Murguía, Mónica Lemus, Elena Roces de Álvarez-Buylla
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...
January 2, 2017: Islets
Amber D Lockridge, Daniel C Baumann, Brian Akhaphong, Alleah Abrenica, Robert F Miller, Emilyn U Alejandro
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)...
November 2016: Islets
Andrew R Pepper, Antonio Bruni, Rena L Pawlick, Boris Gala-Lopez, Yasmin Rafiei, John Wink, Tatsuya Kin, A M James Shapiro
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...
November 2016: Islets
Maciej Sassek, Ewa Pruszynska-Oszmalek, Paweł A Kołodziejski, Dawid Szczepankiewicz, Przemyslaw Kaczmarek, Marianna Wieloch, Katarzyna Kurto, Leszek Nogowski, Krzysztof W Nowak, Mathias Z Strowski, Pawel Mackowiak
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...
November 2016: Islets
Ingrid K Hals, Rinku Singh, Zuheng Ma, Hanne Scholz, Anneli Björklund, Valdemar Grill
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...
November 2016: Islets
Valérie Bergeron, Julien Ghislain, Vincent Poitout
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...
November 2016: Islets
Hye Seung Jung, Yu Mi Kang, Ho Seon Park, Byung Yong Ahn, Hakmo Lee, Min Joo Kim, Jin Young Jang, Sun-Whe Kim
Post-translational modification by bonding of small ubiquitin-like modifier (SUMO) peptides influences various cellular functions, and is regulated by SUMO-specific proteases (SENPs). Several proteins have been suggested to have diverse impact on insulin synthesis and secretion through SUMO modification in β cells. However, the role of SUMO modification in β cell mass has not been established. Here, we examined the changes in expression of Senp in INS1 cells and pancreatic islets under diabetes-relevant stress conditions and associated changes in β cell mass...
November 2016: Islets
Kenjiro Kumano, Hitomi Nishinakamura, Toshiyuki Mera, Takeshi Itoh, Hiroyuki Takahashi, Toshiyoshi Fujiwara, Shohta Kodama
Although current immunosuppression protocols improve the efficacy of clinical allogenic islet transplantation, T cell-mediated allorejection remains unresolved, and major histocompatibility complexes (MHCs) play a crucial role in this process. Papain, a cysteine protease, has the unique ability to cleave the extracellular domain of the MHC class I structure. We hypothesized that pretreatment of donor islets with papain would diminish the expression of MHC class I on islets, reducing allograft immunogenicity and contributing to prolongation of islet allograft survival...
September 2, 2016: Islets
Kazuma Tago, Ken-Ichi Inoue, Motoshi Ouchi, Yoshikazu Miura, Keiichi Kubota
The receptor for advanced glycation endproducts (RAGE) is a pattern recognition receptor that plays an important role in natural immunity. It is suggested that mesenchymal cells are the major players during inflammation. Previously, we reported that advanced glycation end products (AGE), known to be one of the ligands of RAGE, inhibited glucose-induced insulin secretion from ex vivo pancreatic islets, although the mechanism responsible remains largely unknown. In the present study, we examined the cascades operating downstream from RAGE using the insulinoma cell line INS1E and primary-cultured pancreatic fibroblasts as in vitro models for parenchymal (β) cells and mesenchymal cells, respectively...
September 2, 2016: Islets
Joshua A Levine, Kelly A Kaihara, Brian T Layden, Barton Wicksteed
Type 2 diabetes is associated with obesity, insulin resistance and β-cell failure. Therapeutic aims are to reduce adiposity, improve insulin sensitivity and enhance β-cell function. However, it has been proposed that chronically increasing insulin release leads to β-cell exhaustion and failure. We previously developed mice to have increased activity of the cAMP-dependent protein kinase (PKA), specifically in β-cells (β-caPKA mice). β-caPKA mice have enhanced acute phase insulin release, which is the primary determinant of the efficacy of glucose clearance...
September 2, 2016: Islets
Rena L Pawlick, John Wink, Andrew R Pepper, Antonio Bruni, Nasser Abualhassen, Yasmin Rafiei, Boris Gala-Lopez, Mariusz Bral, A M James Shapiro
Quality of life in Type 1 diabetic patients may be improved with islet transplantation, but lifelong immunosuppression is required to prevent rejection. Allo-immune response is a key player in graft dysfunction and although the adaptive immune response is well characterized, the effect of the innate immune reaction after transplantation is only recently becoming appreciated. In this study, we address how the innate response affects long-term outcomes in a murine islet allotransplant model. CTLA-4 Ig treatment is known to significantly prolong kidney subcapsular islet allograft survival and enhance glucose tolerance...
September 2, 2016: Islets
Olga Hrytsenko, Bill Pohajdak, James R Wright
Tilapia, a teleost fish, have multiple large anatomically discrete islets which are easy to harvest, and when transplanted into diabetic murine recipients, provide normoglycemia and mammalian-like glucose tolerance profiles. Tilapia insulin differs structurally from human insulin which could preclude their use as islet donors for xenotransplantation. Therefore, we produced transgenic tilapia with islets expressing a humanized insulin gene. It is now known that fish genomes may possess an ancestral duplication and so tilapia may have a second insulin gene...
July 3, 2016: Islets
Antonio Bruni, Andrew R Pepper, Boris Gala-Lopez, Rena Pawlick, Nasser Abualhassan, James D Crapo, Jon D Piganelli, A M James Shapiro
Islet transplantation is a highly effective treatment for stabilizing glycemic control for select patients with type-1 diabetes. Despite improvements to clinical transplantation, single-donor transplant success has been hard to achieve routinely, necessitating increasing demands on viable organ availability. Donation after circulatory death (DCD) may be an alternative option to increase organ availability however, these organs tend to be more compromised. The use of metalloporphyrin anti-inflammatory and antioxidant (MnP) compounds previously demonstrated improved in vivo islet function in preclinical islet transplantation...
July 3, 2016: Islets
Martijn van de Bunt, Majlinda Lako, Amy Barrett, Anna L Gloyn, Mattias Hansson, Mark I McCarthy, Nicola L Beer, Christian Honoré
Directed differentiation of stem cells offers a scalable solution to the need for human cell models recapitulating islet biology and T2D pathogenesis. We profiled mRNA expression at 6 stages of an induced pluripotent stem cell (iPSC) model of endocrine pancreas development from 2 donors, and characterized the distinct transcriptomic profiles associated with each stage. Established regulators of endodermal lineage commitment, such as SOX17 (log2 fold change [FC] compared to iPSCs = 14.2, p-value = 4.9 × 10(-5)) and the pancreatic agenesis gene GATA6 (log2 FC = 12...
April 18, 2016: Islets
You Jeong Kim, Su Min Park, Hye Sook Jung, Eun Ju Lee, Tae Kyoon Kim, Tae-Nyun Kim, Min Jeong Kwon, Soon Hee Lee, Byoung Doo Rhee, Mi-Kyung Kim, Jeong Hyun Park
BACKGROUND: Ginsenoside Rg3 has been proposed to mediate anti-diabetic effects, but their direct effect on pancreatic β cell viability and mechanisms are not clearly understood. Recent studies suggest that intermittent high glucose (IHG) could be more harmful to pancreatic β cells than sustained high glucose. There are few reports about the effect of the ginsenosideRg3 to β cell apoptosis and proliferation against IHG. METHODS: INS-1 cells were treated with alternative glucose concentration with or without ginsenoside Rg3...
April 18, 2016: Islets
Christine A Beamish, Brenda J Strutt, Edith J Arany, David J Hill
Regeneration of insulin-producing β-cells from resident pancreas progenitors requires an understanding of both progenitor identity and lineage plasticity. One model suggested that a rare β-cell sub-population within islets demonstrated multi-lineage plasticity. We hypothesized that β-cells from young mice (postnatal day 7, P7) exhibit such plasticity and used a model of islet dedifferentiation toward a ductal epithelial-cell phenotype to test this theory. RIPCre;Z/AP(+/+) mice were used to lineage trace the fate of β-cells during dedifferentiation culture by a human placental alkaline phosphatase (HPAP) reporter...
April 18, 2016: Islets
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