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Diabetes,Islet pancreatic cell

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https://read.qxmd.com/read/30776371/ameliorating-gut-microenvironment-through-staphylococcal-nuclease-mediated-intestinal-nets-degradation-for-prevention-of-type-1-diabetes-in-nod-mice
#1
Yixuan Liang, Xiaoke Wang, Dongmei He, Qi You, Tingting Zhang, Wanfa Dong, Jingjin Fei, Yun Xing, Jie Wu
AIMS: Recent studies have revealed that neutrophil extracellular traps (NETs) provide negative feedback in the progression to chronic inflammation and contribute to the pathogenesis of multiple autoimmune diseases including type 1 diabetes (T1D). In addition, accumulating evidences suggest that gut immunity play a key role in T1D pathogenesis. Our study aimed to evaluate whether staphylococcal nuclease (SNase) targeting intestinal NETs can ameliorate the intestinal inflammatory environment and protect against T1D development in non-obese diabetic(NOD) mice...
February 15, 2019: Life Sciences
https://read.qxmd.com/read/30772113/liraglutide-prevents-%C3%AE-cell-apoptosis-via-inactivation-of-nox2-and-its-related-signaling-pathway
#2
Min Ding, Qian-Hua Fang, Yuan-Tao Cui, Qi-Ling Shen, Qian Liu, Peng-Hua Wang, De-Min Yu, Chun-Jun Li
AIMS: High glucose (HG)-induced pancreatic β-cell apoptosis may be a major contributor to the progression of diabetes mellitus (DM). NADPH oxidase (NOX2) has been considered a crucial regulator in β-cell apoptosis. This study was designed to evaluate the impact of GLP-1 receptor agonist (GLP-1Ra) liraglutide on pancreatic β-cell apoptosis in diabetes and the underlying mechanisms involved. METHODS: The diabetic rat models induced by streptozotocin (STZ) and a high fat diet (HFD) received 12 weeks of liraglutide treatment...
January 2, 2019: Journal of Diabetes and its Complications
https://read.qxmd.com/read/30767782/microrna-690-regulates-induced-pluripotent-stem-cells-ipscs-differentiation-into-insulin-producing-cells-by-targeting-sox9
#3
Yang Xu, Yan Huang, Yibing Guo, Yicheng Xiong, Shajun Zhu, Liancheng Xu, Jingjing Lu, Xiaohong Li, Jian Wan, Yuhua Lu, Zhiwei Wang
BACKGROUND: The regulatory mechanism of insulin-producing cells (IPCs) differentiation from induced pluripotent stem cells (iPSCs) in vitro is very important in the phylogenetics of pancreatic islets, the molecular pathogenesis of diabetes, and the acquisition of high-quality pancreatic β-cells derived from stem cells for cell therapy. METHODS: miPSCs were induced for IPCs differentiation. miRNA microarray assays were performed by using total RNA from our iPCs-derived IPCs containing undifferentiated iPSCs and iPSCs-derived IPCSs at day 4, day 14, and day 21 during step 3 to screen the differentially expressed miRNAs (DEmiRNAs) related to IPCs differentiation, and putative target genes of DEmiRNAs were predicted by bioinformatics analysis...
February 15, 2019: Stem Cell Research & Therapy
https://read.qxmd.com/read/30762474/rorb-and-rorc-associate-with-human-islet-dysfunction-and-inhibit-insulin-secretion-in-ins-1-cells
#4
Jalal Taneera, Abdul Khader Mohammed, Sarah Dhaiban, Mawieh Hamad, Rashmi B Prasad, Nabil Sulaiman, Albert Salehi
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...
February 14, 2019: Islets
https://read.qxmd.com/read/30760930/diabetes-relief-in-mice-by-glucose-sensing-insulin-secreting-human-%C3%AE-cells
#5
Kenichiro Furuyama, Simona Chera, Léon van Gurp, Daniel Oropeza, Luiza Ghila, Nicolas Damond, Heidrun Vethe, Joao A Paulo, Antoinette M Joosten, Thierry Berney, Domenico Bosco, Craig Dorrell, Markus Grompe, Helge Ræder, Bart O Roep, Fabrizio Thorel, Pedro L Herrera
Cell-identity switches, in which terminally differentiated cells are converted into different cell types when stressed, represent a widespread regenerative strategy in animals, yet they are poorly documented in mammals. In mice, some glucagon-producing pancreatic α-cells and somatostatin-producing δ-cells become insulin-expressing cells after the ablation of insulin-secreting β-cells, thus promoting diabetes recovery. Whether human islets also display this plasticity, especially in diabetic conditions, remains unknown...
February 13, 2019: Nature
https://read.qxmd.com/read/30760321/the-role-of-the-vasculature-niche-on-insulin-producing-cells-generated-by-transdifferentiation-of-adult-human-liver-cells
#6
Irit Meivar-Levy, Fatima Zoabi, Gil Nardini, Eugenia Manevitz-Mendelson, Gil S Leichner, Oranit Zadok, Michael Gurevich, Eytan Mor, Simona Dima, Irinel Popescu, Aviv Barzilai, Sarah Ferber, Shoshana Greenberger
BACKGROUND: Insulin-dependent diabetes is a multifactorial disorder that could be theoretically cured by functional pancreatic islets and insulin-producing cell (IPC) implantation. Regenerative medicine approaches include the potential for growing tissues and organs in the laboratory and transplanting them when the body cannot heal itself. However, several obstacles remain to be overcome in order to bring regenerative medicine approach for diabetes closer to its clinical implementation; the cells generated in vitro are typically of heterogenic and immature nature and the site of implantation should be readily vascularized for the implanted cells to survive in vivo...
February 13, 2019: Stem Cell Research & Therapy
https://read.qxmd.com/read/30759072/survival-in-a-bad-neighborhood-pancreatic-islets-in-cystic-fibrosis
#7
REVIEW
Andrew W Norris, Katie Larson Ode, Lina Merjaneh, Srinath Sanda, Yaling Yi, Xingshen Sun, John F Engelhardt, Rebecca L Hull
In cystic fibrosis (CF), ductal plugging and acinar loss result in rapid decline of exocrine pancreatic function. This destructive process results in remodeled islets, with only a modest reduction in insulin producing β cells. However, β-cell function is profoundly impaired, with decreased insulin release and abnormal glucose tolerance being present even in infants with CF. Ultimately, roughly half of CF subjects develop diabetes (termed CF-related diabetes, CFRD). Importantly, CFRD increases CF morbidity and mortality via worsening catabolism and pulmonary disease...
February 1, 2019: Journal of Endocrinology
https://read.qxmd.com/read/30755634/synergic-effects-of-oxygen-supply-and-antioxidants-on-pancreatic-%C3%AE-cell-spheroids
#8
Dina Myasnikova, Tatsuya Osaki, Kisaki Onishi, Tatsuto Kageyama, Binbin Zhang Molino, Junji Fukuda
Diabetes is one of the most common metabolic disorders, and is characterized by the inability to secrete/sense insulin and abnormal blood glucose concentration. Many researchers have concentrated their efforts on improving islet transplantation, in particular by fabricating bioartificial pancreatic islets in vitro. One of the critical points for the success of this research direction is the improvement of culture conditions, such as oxygen supply, in the engineering of bioartificial pancreatic islets to ensure their viability and functionality after transplantation...
February 12, 2019: Scientific Reports
https://read.qxmd.com/read/30748094/alginate-microencapsulation-of-human-stem-cell-derived-%C3%AE-cells-with-cxcl12-prolongs-their-survival-and-function-in-immunocompetent-mice-without-systemic-immunosuppression
#9
David A Alagpulinsa, Jenny J L Cao, Riley K Driscoll, Ruxandra F Sîrbulescu, Madeline F E Penson, Marinko Sremac, Elise N Engquist, Timothy A Brauns, James F Markmann, Douglas A Melton, Mark C Poznansky
Pancreatic β-cell replacement by islet transplantation for the treatment of Type 1 Diabetes (T1D) is currently limited by donor tissue scarcity and the requirement for lifelong immunosuppression. The advent of in vitro differentiation protocols for generating functional β-like cells from human pluripotent stem cells, so-called SC-β cells, could eliminate these obstacles. To avoid the need for immunosuppression, alginate-microencapsulation is widely investigated as a safe path to β-cell replacement. Nonetheless, inflammatory foreign body responses leading to pericapsular fibrotic overgrowth often causes microencapsulated islet-cell death and graft failure...
February 12, 2019: American Journal of Transplantation
https://read.qxmd.com/read/30742993/impact-of-apolipoprotein-a1-or-lecithin-cholesterol-acyltransferase-deficiency-on-white-adipose-tissue-metabolic-activity-and-glucose-homeostasis-in-mice
#10
Eva Xepapadaki, Giuseppe Maulucci, Caterina Constantinou, Eleni A Karavia, Evangelia Zvintzou, Bareket Daniel, Shlomo Sasson, Kyriakos E Kypreos
High density lipoprotein (HDL) has attracted the attention of biomedical community due to its well-documented role in atheroprotection. HDL has also been recently implicated in the regulation of islets of Langerhans secretory function and in the etiology of peripheral insulin sensitivity. Indeed, data from numerous studies strongly indicate that the functions of pancreatic β-cells, skeletal muscles and adipose tissue could benefit from improved HDL functionality. To better understand how changes in HDL structure may affect diet-induced obesity and type 2 diabetes we aimed at investigating the impact of Apoa1 or Lcat deficiency, two key proteins of peripheral HDL metabolic pathway, on these pathological conditions in mouse models...
February 8, 2019: Biochimica et biophysica acta. Molecular basis of disease
https://read.qxmd.com/read/30741587/-intracellular-cytosolic-complement-component-c3-regulates-cytoprotective-autophagy-in-pancreatic-beta-cells-by-interaction-with-atg16l1
#11
Ben C King, Erik Renström, Anna M Blom
Complement component C3 is central to the complement system, a humoral effector mechanism of innate immune defense. When activated, C3 covalently binds to target particles, marking them for uptake and clearance by phagocytosis. We now show that C3 also exists within the cytosol where it interacts with ATG16L1, and is therefore involved in the intracellular clearance and recycling of material by macroautophagy/autophagy in pancreatic beta cells. C3 is highly expressed in isolated human islets, and its expression is upregulated in islets isolated from diabetic patients and rodents, and correlates with patient HBA1c and body mass index (BMI)...
February 11, 2019: Autophagy
https://read.qxmd.com/read/30738185/paving-the-way-for-successful-islet-encapsulation
#12
REVIEW
Nikos Dimitrioglou, Maria Kanelli, Efstathia Papageorgiou, Theodore Karatzas, Dimitris Hatziavramidis
Type 1 diabetes mellitus (T1DM) is a disorder that decimates pancreatic β-cells which produce insulin. Direct pancreatic islet transplantation cannot serve as a widespread therapeutic modality owing to the need for lifelong immunosuppression and donor shortage. Therefore, several encapsulation techniques have been developed to enclose the islets in semipermeable vehicles that will allow oxygen and nutrient input as well as insulin, other metabolites and waste output, while accomplishing immunoisolation. Although encapsulation technology continues to face significant obstacles, recent advances in material science, stem cell biology and immunology potentially serve as pathways to success...
February 6, 2019: Drug Discovery Today
https://read.qxmd.com/read/30736905/multilineage-potential-research-on-pancreatic-mesenchymal-stem-cells-of-bovine
#13
Fan Gao, Yangnan Wu, Hebao Wen, Wanwan Zhu, Han Ren, Weijun Guan, Xiuzhi Tian
Stem cells are most likely to solve all three of diabetes's problems at once, but the previous studies have mostly focused on bone marrow mesenchymal stem cells (MSCs) and adipose tissue-derived MSCs, and few studies have been done on pancreatic MSCs. In this study, pancreatic was collected to isolate MSCs from bovine, and then their biological characteristics such as growth kinetics, surface antigen, and multilineage potential were examined. Pancreatic MSCs of bovine (B-PMSCs) could be cultured for 65 passages in vitro...
February 2019: Tissue & Cell
https://read.qxmd.com/read/30721151/epigenetic-modulation-of-%C3%AE-cells-by-interferon-%C3%AE-via-pnpt1-mir26a-tet2-triggers-autoimmune-diabetes
#14
Mihaela Stefan-Lifshitz, Esra Karakose, Lingguang Cui, Abora Ettela, Zhengzi Yi, Weijia Zhang, Yaron Tomer
Type 1 diabetes (T1D) is caused by autoimmune destruction of pancreatic β cells. Mounting evidence supports a central role for β-cell alterations in triggering the activation of self-reactive T-cells in T1D. However, the early deleterious events that occur in β cells, underpinning islet autoimmunity are not known. We hypothesized that epigenetic modifications induced in β cells by inflammatory mediators play a key role in initiating the autoimmune response. We analyzed DNA methylation (DNAm) patterns and gene expression in human islets exposed to IFNα, a cytokine associated with T1D development...
February 5, 2019: JCI Insight
https://read.qxmd.com/read/30721137/defective-exocytosis-and-processing-of-insulin-in-a-cystic-fibrosis-mouse-model
#15
Anna Edlund, Mohammad Barghouth, Michael Huhn, Mia Abels, Jonathan Esguerra, Ines Mollet, Emma Svedin, Anna Wendt, Erik Renstrom, Enming Zhang, Nils Wierup, Bob J Scholte, Malin Flodström-Tullberg, Lena Eliasson
Cystic fibrosis-related diabetes (CFRD) is a common complication for patients with cystic fibrosis (CF), a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). The cause of CFRD is unclear, but a commonly observed reduction in first-phase insulin secretion suggests defects at the beta cell level. Here we aimed to examine beta- and alpha-cell function in the Cftrtm1EUR/F508del mouse model (C57BL/6J), which carries the most common human mutation in CFTR, the F508del mutation...
February 1, 2019: Journal of Endocrinology
https://read.qxmd.com/read/30720465/%C3%AE-cell-tone-is-defined-by-proglucagon-peptides-through-cyclic-amp-signaling
#16
Megan E Capozzi, Berit Svendsen, Sara E Encisco, Sophie L Lewandowski, Mackenzie D Martin, Haopeng Lin, Justin L Jaffe, Reilly W Coch, Jonathan M Haldeman, Patrick E MacDonald, Matthew J Merrins, David A D'Alessio, Jonathan E Campbell
Paracrine interactions between pancreatic islet cells have been proposed as a mechanism to regulate hormone secretion and glucose homeostasis. Here, we demonstrate the importance of proglucagon-derived peptides (PGDPs) for α- to β-cell communication and control of insulin secretion. Signaling through this system occurs through both the glucagon-like peptide receptor (Glp1r) and glucagon receptor (Gcgr). Loss of PGDPs, or blockade of their receptors, decreases insulin secretion in response to both metabolic and non-metabolic stimulation of mouse and human islets...
February 5, 2019: JCI Insight
https://read.qxmd.com/read/30719867/concise-review-canine-diabetes-mellitus-as-a-translational-model-for-innovative-regenerative-medicine-approaches
#17
REVIEW
Maryam Moshref, Bonnie Tangey, Chen Gilor, Klearchos K Papas, Peter Williamson, Lindsey Loomba-Albrecht, Paul Sheehy, Amir Kol
Diabetes mellitus (DM) is a common spontaneous endocrine disorder in dogs, which is defined by persistent hyperglycemia and insulin deficiency. Like type 1 diabetes (T1D) in people, canine DM is a complex and multifactorial disease in which genomic and epigenomic factors interact with environmental cues to induce pancreatic β-cell loss and insulin deficiency, although the pathogenesis of canine DM is poorly defined and the role of autoimmunity is further controversial. Both diseases are incurable and require life-long exogenous insulin therapy to maintain glucose homeostasis...
February 5, 2019: Stem Cells Translational Medicine
https://read.qxmd.com/read/30719525/engineering-human-islet-organoids-from-ipscs-using-an-organ-on-chip-platform
#18
Tingting Tao, Yaqing Wang, Wenwen Chen, Zhongyu Li, Wentao Su, Yaqiong Guo, Pengwei Deng, Jianhua Qin
Human pluripotent stem cell (hPSC)-derived islet cells provide promising resources for diabetes studies, cell replacement treatment and drug screening. Recently, hPSC-derived organoids have represented a new class of in vitro organ models for disease modeling and regenerative medicine. However, rebuilding biomimetic human islet organoids from hPSCs remains challenging. Here, we present a new strategy to engineer human islet organoids derived from human induced pluripotent stem cells (hiPSCs) using an organ-on-a-chip platform combined with stem cell developmental principles...
February 5, 2019: Lab on a Chip
https://read.qxmd.com/read/30715843/glycated-insulin-exacerbates-the-cytotoxicity-of-human-islet-amyloid-polypeptides-a-vicious-cycle-in-type-2-diabetes
#19
Liang Ma, Chen Yang, Lianqi Huang, Yuchen Chen, Yang Li, Cheng Cheng, Biao Cheng, Ling Zheng, Kun Huang
The aggregation of human islet amyloid polypeptide (hIAPP) is one of the triggering factors of type 2 diabetes mellitus (T2DM). hIAPP is co-synthesized, co-stored and co-secreted with insulin in pancreatic β-cells, and insulin inhibits hIAPP aggregation. In T2DM patients, long-term hyperglycemia causes glycation of near 10% of total insulin. The glycation not only modifies insulin but also crosslinks insulin into oligomers. However, the effect of glycated human insulin on hIAPP aggregation is unknown. In this study, four physiologically relevant monosaccharides, methylglyoxal, glucose, fructose and ribose were used to glycate human insulin and two C-terminus truncated insulin analogues...
February 4, 2019: ACS Chemical Biology
https://read.qxmd.com/read/30713110/multiplexed-in-situ-imaging-mass-cytometry-analysis-of-the-human-endocrine-pancreas-and-immune-system-in-type-1-diabetes
#20
Yue J Wang, Daniel Traum, Jonathan Schug, Long Gao, Chengyang Liu, Mark A Atkinson, Alvin C Powers, Michael D Feldman, Ali Naji, Kyong-Mi Chang, Klaus H Kaestner
The interaction between the immune system and endocrine cells in the pancreas is crucial for the initiation and progression of type 1 diabetes (T1D). Imaging mass cytometry (IMC) enables multiplexed assessment of the abundance and localization of more than 30 proteins on the same tissue section at 1-μm resolution. Herein, we have developed a panel of 33 antibodies that allows for the quantification of key cell types including pancreatic exocrine cells, islet cells, immune cells, and stromal components. We employed this panel to analyze 12 pancreata obtained from donors with clinically diagnosed T1D and 6 pancreata from non-diabetic controls...
January 28, 2019: Cell Metabolism
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