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https://www.readbyqxmd.com/read/28719653/isolation-of-a-monoclonal-antibody-from-a-phage-display-library-binding-the-rhesus-macaque-mhc-class-i-allomorph-mamu-a1-001
#1
Nathan Holman, Jason T Weinfurter, Trevor R Harsla, Roger W Wiseman, Aaron J Belli, Anthony J Michaels, Keith A Reimann, Robert I DeMars, Matthew R Reynolds
Monoclonal antibodies that bind to human leukocyte antigen (HLA) are useful tools for HLA-typing, tracking donor-recipient chimerisms after bone marrow transplants, and characterizing specific major histocompatibility complexes (MHC) on cell surfaces. Unfortunately, equivalent reagents are not available for rhesus macaques, which are commonly used animal as models in organ transplant and infectious disease research. To address this deficiency, we isolated an antibody that recognizes the common Indian rhesus macaque MHC class I molecule, Mamu-A1*001...
2017: PloS One
https://www.readbyqxmd.com/read/28647274/sonic-hedgehog-pathway-suppression-and-reactivation-accelerates-differentiation-of-rat-adipose-derived-mesenchymal-stromal-cells-toward-insulin-producing-cells
#2
Dian Dayer, Mahmoud Hashemi Tabar, Eskandar Moghimipour, Mohammad Reza Tabandeh, Ata A Ghadiri, Elham Allah Bakhshi, Mahmoud Orazizadeh, Mohammad Ali Ghafari
BACKGROUND AIMS: Sonic hedgehog (Shh) is an intercellular signaling molecule that regulates pancreas development in mammals. Manipulation of Shh signaling pathway can be used as reliable approach to improve the generation of functional insulin-producing cells (IPCs) from mesenchymal stromal cells (MSCs). METHODS: In the present study, a novel differentiation protocol was used to produce IPCs from adipose tissue-derived MSCs (ATDMSCs) based on sequential inhibition and reactivation of Shh pathway...
June 21, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28624907/dityrosine-administration-induces-dysfunction-of-insulin-secretion-accompanied-by-diminished-thyroid-hormones-t3-function-in-pancreas-of-mice
#3
Yin-Yi Ding, Zhu-Qing Li, Xiang-Rong Cheng, Yu-Mei Ran, Sha-Ji Wu, Yonghui Shi, Guowei Le
Oxidized tyrosine products are commonly found in food with high protein content and have been demonstrated to cause damage of liver and kidney in our previous studies. Dityrosine (Dityr) is a typical oxidized tyrosine product. Due to its structural homology with thyroid hormones T3, we assumed that one of the endocrine systems most likely considered in connection with its disruption by Dityr may be the T3 action. T3 plays important roles in insulin synthesis, and thyroid hormone resistance (RTH) is associated with the impairment of glucose metabolism...
June 17, 2017: Amino Acids
https://www.readbyqxmd.com/read/28487936/protein-therapy-using-mafa-fused-to-a-polyarginine-transduction-domain-attenuates-glucose-levels-of-streptozotocin%C3%A2-induced-diabetic-mice
#4
Jun Lu, Lingjing Lin, Huiyue Dong, Xin Meng, Fang Fang, Qinghua Wang, Lianghu Huang, Jianming Tan
Ectopic expression of musculo aponeurotic fibrosarcoma BZIP transcription factor (Maf) A, has previously been demonstrated to induce insulin expression in non‑β‑cell lines. Protein transduction domains acting as an alternative delivery strategy may deliver heterogeneous proteins into cells. A sequence of 11 arginine residues (11R) has been demonstrated to act as a particularly efficient vector to introduce proteins into various cell types. The present study constructed 11R‑fused MafA to achieve transduction of the protein into cellular membranes and subsequently examined the therapeutic effect of the MafA‑11R protein in streptozotocin‑induced diabetes...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28479244/role-of-pi3k-p110%C3%AE-in-the-differentiation-of-human-embryonic-stem-cells-into-islet-like-cells
#5
Gen-Hong Mao, Ping Lu, Ya-Nan Wang, Chen-Guang Tian, Xiao-Hui Huang, Zong-Gang Feng, Jin-Lan Zhang, Hong-Yang Chang
To investigate the effects of the PI3K inhibitors on the differentiation of insulin-producing cells derived from human embryonic stem cells. Here, we report that human embryonic stem cells induced by phosphatidylinositol-3-kinase (PI3K) p110β inhibitors could produce more mature islet-like cells. Findings were validated by immunofluorescence analysis, quantitative real-time PCR, insulin secretion in vitro and cell transplantation for the diabetic SCID mice. Immunofluorescence analysis revealed that unihormonal insulin-positive cells were predominant in cultures with rare polyhormonal cells...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28432716/deciphering-tacrolimus-induced-toxicity-in-pancreatic-%C3%AE-cells
#6
J Triñanes, A E Rodriguez-Rodriguez, Y Brito-Casillas, A Wagner, A P J De Vries, G Cuesto, A Acebes, E Salido, A Torres, E Porrini
β-cell transcription factors like: FoxO1, MafA, PDX-1, NeuroD, are dysfunctional in type 2 diabetes (T2DM). PTDM resembles T2DM and reflects interaction between pre-transplant insulin resistance and immunosuppressants, mainly calcineurin inhibitors. We evaluated the effect of tacrolimus, cyclosporine-A and metabolic stressors (glucose+palmitate) on insulinoma β-cells (INS-1) in vitro and in pancreata of obese and lean Zucker rats. Cells were cultured for five days with 100μM palmitate and 22mM glucose; cyclosporin-A (250ng/mL) or tacrolimus (15ng/mL) were added the last 48h...
April 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28424732/evidence-for-loss-in-identity-de-differentiation-and-trans-differentiation-of-islet-%C3%AE-cells-in-type-2-diabetes
#7
REVIEW
Chad S Hunter, Roland W Stein
The two main types of diabetes mellitus have distinct etiologies, yet a similar outcome: loss of islet β-cell function that is solely responsible for the secretion of the insulin hormone to reduce elevated plasma glucose toward euglycemic levels. Type 1 diabetes (T1D) has traditionally been characterized by autoimmune-mediated β-cell death leading to insulin-dependence, whereas type 2 diabetes (T2D) has hallmarks of peripheral insulin resistance, β-cell dysfunction, and cell death. However, a growing body of evidence suggests that, especially during T2D, key components of β-cell failure involves: (1) loss of cell identity, specifically proteins associated with mature cell function (e...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28424159/prolonged-elimination-of-negative-feedback-control-mechanisms-along-the-insulin-signaling-pathway-impairs-%C3%AE-cell-function-in-vivo
#8
Roi Isaac, Yaron Vinik, Sigalit Boura-Halfon, Lydia Farack, Sarina Streim, Eytan Elhanany, Zvi Kam, Yehiel Zick
Cellular stress and proinflammatory cytokines induce phosphorylation of insulin receptor substrate (IRS) proteins at Ser sites that inhibit insulin and IGF-I signaling. We therefore examined the effects of mutation of five "inhibitory" Ser phosphorylation sites on IRS2 function in transgenic mice that overexpress, selectively in pancreatic β-cells, either wild-type (WT) or a mutated IRS2 protein (IRS2(5A)). Islets size, number, and mRNA levels of catalase and superoxide dismutase were increased, whereas those of nitric oxide synthase were decreased, in 7- to 10-week-old IRS2(5A)-β mice compared with IRS2(WT)-β mice...
July 2017: Diabetes
https://www.readbyqxmd.com/read/28420418/adult-muscle-derived-stem-cells-engraft-and-differentiate-into-insulin-expressing-cells-in-pancreatic-islets-of-diabetic-mice
#9
Violeta Mitutsova, Wendy Wai Yeng Yeo, Romain Davaze, Celine Franckhauser, El-Habib Hani, Syahril Abdullah, Patrice Mollard, Marie Schaeffer, Anne Fernandez, Ned J C Lamb
BACKGROUND: Pancreatic beta cells are unique effectors in the control of glucose homeostasis and their deficiency results in impaired insulin production leading to severe diabetic diseases. Here, we investigated the potential of a population of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to differentiate in vitro into beta cells when transplanted as undifferentiated stem cells in vivo to compensate for beta-cell deficiency. RESULTS: In vitro, cultured MDSC spontaneously differentiated into insulin-expressing islet-like cell clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry under the control of an insulin promoter...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28381388/pancreaticoduodenectomy-for-borderline-resectable-pancreatic-head-cancer-with-a-modified-artery-first-approach-technique
#10
Min Wang, Hang Zhang, Feng Zhu, Feng Peng, Xin Wang, Ming Shen, Ren-Yi Qin
BACKGROUND: The treatment of borderline resectable pancreatic head cancer (BRPHC) is still controversial and challenging. The artery-first approaches are described to be the important options for the early determination. Whether these approaches can achieve an increase R0 rate, better bleeding control and increasing long-term survival for BRPHC are still controversial. We compared a previously reported technique, a modified artery-first approach (MAFA), with conventional techniques for the surgical treatment of BRPHC...
April 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/28377501/the-transcription-factor-pax6-is-required-for-pancreatic-%C3%AE-cell-identity-glucose-regulated-atp-synthesis-and-ca-2-dynamics-in-adult-mice
#11
Ryan K Mitchell, Marie-Sophie Nguyen-Tu, Pauline Chabosseau, Rebecca M Callingham, Timothy J Pullen, Rebecca Cheung, Isabelle Leclerc, David J Hodson, Guy A Rutter
Heterozygous mutations in the human paired box gene PAX6 lead to impaired glucose tolerance. Although embryonic deletion of the Pax6 gene in mice leads to loss of most pancreatic islet cell types, the functional consequences of Pax6 loss in adults are poorly defined. Here we developed a mouse line in which Pax6 was selectively inactivated in β cells by crossing animals with floxed Pax6 alleles to mice expressing the inducible Pdx1CreERT transgene. Pax6 deficiency, achieved by tamoxifen injection, caused progressive hyperglycemia...
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28363269/establishing-a-large-animal-model-for-in-vivo-reprogramming-of-bile-duct-cells-into-insulin-secreting-cells-to-treat-diabetes
#12
Caitlin M Hill, Anannya Banga, Juan E Abrahante, Ce Yuan, Lucas A Mutch, Jody Janecek, Timothy O'Brien, Melanie L Graham, James R Dutton
Type 1 diabetes manifests as autoimmune destruction of beta cells requiring metabolic management with an exogenous replacement of insulin, either by repeated injection of recombinant insulin or by transplantation of allogeneic islets from cadaveric donors. Both of these approaches have severe limitations. Repeated insulin injection requires intensive blood glucose monitoring, is expensive, and is associated with decreased quality-of-life measures. Islet transplantation, while highly effective, is severely limited by shortage of donor organs...
June 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28290604/glucagon-like-peptide-1-receptor-agonist-ameliorates-the-insulin-resistance-function-of-islet-%C3%AE-cells-via-the-activation-of-pdx-1-jak-signaling-transduction-in-c57-bl6-mice-with-high-fat-diet-induced-diabetes
#13
Tao Hao, Hongtao Zhang, Sheyu Li, Haoming Tian
Long-term exposure to a high-fat diet (HFD) causes glucotoxicity and lipotoxicity in islet β cells and leads to the development of metabolic dysfunctions. Reductions in pancreatic and duodenal homeobox-1 (PDX-1) expression have been shown to induce type 2 diabetes mellitus by causing impairments to islet β cells. Glucagon-like peptide 1 (GLP-1) treatment reduces endogenous insulin resistance in HFD-induced type 2 diabetes mellitus. In the present study, the underlying mechanism by which GLP-1 exerts its function in type 2 diabetes mellitus was investigated...
April 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28270834/metabolic-stress-and-compromised-identity-of-pancreatic-beta-cells
#14
REVIEW
Avital Swisa, Benjamin Glaser, Yuval Dor
Beta cell failure is a central feature of type 2 diabetes (T2D), but the molecular underpinnings of the process remain only partly understood. It has been suggested that beta cell failure in T2D involves massive cell death. Other studies ascribe beta cell failure to cell exhaustion, due to chronic oxidative or endoplasmic reticulum stress leading to cellular dysfunction. More recently it was proposed that beta cells in T2D may lose their differentiated identity, possibly even gaining features of other islet cell types...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28223284/mafa-enables-pdx1-to-effectively-convert-pancreatic-islet-progenitors-and-committed-islet-%C3%AE-cells-into-%C3%AE-cells-in-vivo
#15
Taka-Aki Matsuoka, Satoshi Kawashima, Takeshi Miyatsuka, Shugo Sasaki, Naoki Shimo, Naoto Katakami, Dan Kawamori, Satomi Takebe, Pedro L Herrera, Hideaki Kaneto, Roland Stein, Iichiro Shimomura
Among the therapeutic avenues being explored for replacement of the functional islet β-cell mass lost in type 1 diabetes (T1D), reprogramming of adult cell types into new β-cells has been actively pursued. Notably, mouse islet α-cells will transdifferentiate into β-cells under conditions of near β-cell loss, a condition similar to T1D. Moreover, human islet α-cells also appear to poised for reprogramming into insulin-positive cells. Here we have generated transgenic mice conditionally expressing the islet β-cell-enriched Mafa and/or Pdx1 transcription factors to examine their potential to transdifferentiate embryonic pan-islet cell Ngn3-positive progenitors and the later glucagon-positive α-cell population into β-cells...
May 2017: Diabetes
https://www.readbyqxmd.com/read/28152182/reprogramming-of-pancreatic-acinar-cells-to-functional-beta-cells-by-in-vivo-transduction-of-a-polycistronic-construct-containing-pdx1-ngn3-mafa-in-mice
#16
C Cavelti-Weder, A Zumsteg, W Li, Q Zhou
To generate new beta cells after birth is a key focus of regenerative medicine, which could greatly aid the major health burden of diabetes. Beta-cell regeneration has been described using four different approaches: (1) the development of beta cells from putative precursor cells of the adult pancreas, which is termed neogenesis, (2) replication of existing beta cells, (3) differentiation from embryonic or induced pluripotent stem cells, and (4) reprogramming of non-beta cells to beta cells. Studies from the authors' laboratory have shown that beta-cell reprogramming can be achieved by transduction of adult pancreatic tissues with viral constructs containing the three developmentally important transcription factors Pdx1, Ngn3, and MafA...
February 2, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/28100871/in-vivo-direct-reprogramming-of-liver-cells-to-insulin-producing-cells-by-virus-free-overexpression-of-defined-factors
#17
Xiao-Fei Yang, Li-Wei Ren, Lu Yang, Chun-Yan Deng, Fu-Rong Li
Direct reprogramming of autologous cells from diabetes patients to insulin producing cells is a new method for pancreatic cell replacement therapy. At present, transdifferentiation among mature cells is achieved mainly by introducing foreign genes into the starting tissue with viral vector, but there are potentical safety problems. In the present study, we delivered plasmids carrying Pdx1, Neurog3 and MafA genes (PNM) into mouse hepatocytes by hydrodynamics tail vein injection, investigated islet β cells markers in transfected cells from protein and mRNA level, and then observed the long-term control of blood glucose in diabetic mice...
March 31, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28078358/major-histocompatibility-complex-haplotyping-and-long-amplicon-allele-discovery-in-cynomolgus-macaques-from-chinese-breeding-facilities
#18
Julie A Karl, Michael E Graham, Roger W Wiseman, Katelyn E Heimbruch, Samantha M Gieger, Gaby G M Doxiadis, Ronald E Bontrop, David H O'Connor
Very little is currently known about the major histocompatibility complex (MHC) region of cynomolgus macaques (Macaca fascicularis; Mafa) from Chinese breeding centers. We performed comprehensive MHC class I haplotype analysis of 100 cynomolgus macaques from two different centers, with animals from different reported original geographic origins (Vietnamese, Cambodian, and Cambodian/Indonesian mixed-origin). Many of the samples were of known relation to each other (sire, dam, and progeny sets), making it possible to characterize lineage-level haplotypes in these animals...
April 2017: Immunogenetics
https://www.readbyqxmd.com/read/28017717/preserving-expression-of-pdx1-improves-%C3%AE-cell-failure-in-diabetic-mice
#19
Yuichi Yamamoto, Takeshi Miyatsuka, Shugo Sasaki, Kazuyuki Miyashita, Fumiyo Kubo, Naoki Shimo, Satomi Takebe, Hirotaka Watada, Hideaki Kaneto, Taka-Aki Matsuoka, Iichiro Shimomura
Pdx1, a β-cell-specific transcription factor, has been shown to play a crucial role in maintaining β-cell function through transactivation of β-cell-related genes. In addition, it has been reported that the expression levels of Pdx1 are compromised under diabetic conditions in human and rodent models. We therefore aimed to clarify the possible beneficial role of Pdx1 against β-cell failure and generated the transgenic mouse that expressed Pdx1 conditionally and specifically in β cells (βPdx1) and crossed these mice with Ins2(Akita) diabetic mice...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27960594/development-of-islet-organoids-from-h9-human-embryonic-stem-cells-in-biomimetic-3d-scaffolds
#20
Weiwei Wang, Sha Jin, Kaiming Ye
Success in the differentiating human embryonic stem cells (hESCs) into insulin-secreting β cells raises new hopes for diabetes treatment. In this work, we demonstrated the feasibility of developing islet organoids from hESCs within biomimetic 3D scaffolds. We showed that such a 3D microenvironment is critical to the generation of pancreatic endoderm and endocrine from hESCs. The organoids formed consisted of pancreatic α, β, δ, and pancreatic polypeptide (PP) cells. A high-level co-expression of PDX1, NKX6...
March 15, 2017: Stem Cells and Development
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