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Pancreas beta cells

B Antonioli, M Galuzzi
First clinical islet allotransplantation in patients affected by type 1 diabetes mellitus was performed about 30 years ago. Despite the progressive improvement of the success rate, the clinical indication to the islet allotransplantation remains limited to selected patients affected by brittle type 1 diabetes mellitus. The burden of the immunosuppression therapy still represents the main critical issue but other areas might be subject to further improvements, such as the islet production, islet engraftment and long-term function...
March 2018: European Review for Medical and Pharmacological Sciences
Kalyani Raju, Srinivas Murthy Venkataramappa
Hemochromatosis is an autosomal recessive genetic disorder resulting in increased intestinal absorption of iron and eventually to iron overload. The onset of symptoms is usually seen around 40 years of age. Iron overload causes tissue damage in liver, pancreas, skin, joints, heart, and gonads. Approximately 50% of patients diagnosed with hemochromatosis will have either type 1 or type 2 diabetes mellitus (DM) because of selective beta-cell damage due to iron overload and leads to impaired insulin synthesis, release, and insulin resistance...
January 2018: International Journal of Applied and Basic Medical Research
Katarzyna Skrzypek, Yazmin Brito Barrera, Thomas Groth, Dimitrios Stamatialis
INTRODUCTION: Encapsulation of pancreatic islets or beta cells is a promising strategy for treatment of type 1 diabetes by providing an immune isolated environment and allowing for transplantation in a different location than the liver. However, islets used for encapsulation often show lower functionality due to the damaging of islet endothelial cells during the isolation procedure. Factors produced by endothelial cells have great impact on beta cell insulin secretion. Therefore, mutual signaling between endothelial cells and beta cells should be considered for the development of encapsulation systems to achieve high insulin secretion and maintain beta cell viability...
March 2018: International Journal of Artificial Organs
Mirhane Hassan, Hala M Raslan, Hesham Gamal Eldin, Eman Mahmoud, Hanaa Alm-Elhuda Abd Elwajed
INTRODUCTION: Type 1 Diabetes Mellitus (T1D) is an autoimmune disease that results from the destruction of insulin-producing beta cells of the pancreas by autoreactive T cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that can potently suppress T cell responses. AIM: To detect the presence of MDSCs in T1D and compare their percentage in T1D versus healthy individuals. METHOD: Thirty T1D patients were included in the study...
February 15, 2018: Open Access Macedonian Journal of Medical Sciences
Marta Fontcuberta-PiSunyer, Sara Cervantes, Eulàlia Miquel, Sergio Mora-Castilla, Louise C Laurent, Angel Raya, Ramon Gomis, Rosa Gasa
Posttranscriptional modifications of histones constitute an epigenetic mechanism that is closely linked to both gene silencing and activation events. Trimethylation of Histone3 at lysine 27 (H3K27me3) is a repressive mark that associates with developmental gene regulation during differentiation programs. In the developing pancreas, expression of the transcription factor Neurogenin3 in multipotent progenitors initiates endocrine differentiation that culminates in the generation of all pancreatic islet cell lineages, including insulin-producing beta cells...
March 9, 2018: Biochimica et Biophysica Acta
Jennifer Rieusset
The contact sites that the endoplasmic reticulum (ER) forms with mitochondria, called mitochondria-associated membranes (MAMs), are a hot topic in biological research, and both their molecular determinants and their numerous roles in several signaling pathways are is continuously evolving. MAMs allow the exchange between both organelles of lipids, calcium (Ca2+ ), and likely reactive oxygen species, allowing adaptations of both cellular bioenergetics and cell fate depending of cellular needs or stresses. Therefore, it is not surprising that MAMs affect cellular metabolism...
March 9, 2018: Cell Death & Disease
Yunxia O'Malley, Pavana G Rotti, Ian M Thornell, Oriana G Vanegas Calderón, Christopher Febres-Aldana, Katelin Durham, Jianrong Yao, Xiaopeng Li, Zheng Zhu, Andrew W Norris, Joseph Zabner, John F Engelhardt, Aliye Uc
Pancreatic ductular epithelial cells comprise the majority of duct cells in pancreas, control cystic fibrosis transmembrane conductance regulator (CFTR)-dependent bicarbonate [HCO3 - ] secretion, but are difficult to grow as a polarized monolayer. Using NIH-3T3-J2 fibroblast feeder cells and a Rho-associated kinase inhibitor, we produced well-differentiated and polarized porcine pancreatic ductular epithelial cells. Cells grown on semipermeable filters at air-liquid interface (ALI) developed typical epithelial cell morphology and stable transepithelial resistance (TER), expressed epithelial cell markers (zona occludens-1 and beta catenin), duct cell markers (SOX-9 and CFTR), but no acinar (amylase) or islet cell (chromogranin) markers...
March 8, 2018: Journal of Applied Physiology
Sarah E Brown, Karilyn E Sant, Shana M Fleischman, Olivia Venezia, Monika A Roy, Ling Zhao, Alicia R Timme-Laragy
BACKGROUND: Butylparaben (butyl p-hydroxybenzoic acid) is a common cosmetic and pharmaceutical preservative reported to induce oxidative stress and endocrine disruption. Embryonic development is sensitive to oxidative stress, with redox potentials playing critical roles in progenitor cell fate decisions. Because pancreatic beta cells have been reported to have low antioxidant gene expression, they may be sensitive targets of oxidative stress. We tested the hypotheses that butylparaben causes oxidative stress in the developing embryo, and that pancreatic beta cells are a sensitive target of butylparaben embryotoxicity...
March 8, 2018: Birth Defects Research
Lorenzo Piemonti, Eelco J P de Koning, Thierry Berney, Jon S Odorico, James F Markmann, Peter G Stock, Michael R Rickels
Defined outcomes for beta cell replacement therapy in the treatment of diabetes are critically needed. Progress towards the clinical acceptance of pancreas and islet transplantation has been hampered by the lack of clear definitions of functional and efficacy outcomes, as well as a lack of consistently applied glycaemic control metrics, together with poor alignment with the field of artificial insulin delivery/artificial pancreas development. To address this problem, the International Pancreas & Islet Transplant Association (IPITA) collaborated with the European Pancreas and Islet Transplant Association (EPITA) to develop a consensus for a joint statement on the definition of function and failure of beta cell replacement therapies, which is summarised in this commentary...
March 6, 2018: Diabetologia
Liansheng Liu, Yaohui Zhu, Michaël Noë, Qian Li, Pankaj Jay Pasricha
BACKGROUND & AIMS: Chronic pancreatitis (CP) is characterized by pancreatic inflammation and fibrosis, associated with increased pancreatic expression of transforming growth factor beta (TGFB). It is not clear how these might contribute to pain. We investigated whether TGFB signaling via SMAD induces sensitization of pancreatic sensory neurons to increase nociception. METHODS: CP was induced in Sprague-Dawley rats by infusion of trinitrobenzene sulfonic acid; some rats were given intrathecal infusions of TGFB1...
March 2, 2018: Gastroenterology
Taedong Han, Byoung Moon Lee, Yoo Hoi Park, Dong Hoon Lee, Hyun Ho Choi, Taehoon Lee, Hakwon Kim
G protein-coupled receptor 119 (GPR119) is expressed in the pancreas and gastrointestinal tract, and its activation promotes insulin secretion in the beta cells of the pancreatic islets as well as the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells, consequently improving glucose-stimulated insulin secretion. Due to this dual mechanism of action, the development of small-molecule GPR119 agonists has received significant interest for the treatment of type 2 diabetes. We newly synthesized 1,2,4-triazolone derivatives of GPR119 agonists, which demonstrated excellent outcomes in a cyclic adenosine monophosphate (cAMP) assay...
March 1, 2018: Biomolecules & Therapeutics
Koji Nakashima, Hideaki Kaneto, Masashi Shimoda, Tomohiko Kimura, Kohei Kaku
Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion from pancreatic beta cells and suppresses glucagon secretion from alpha cells. It remains controversial, however, whether GLP-1 receptor (GLP-1R) is expressed in mature alpha cells. In this study, unlike previous studies using non-diabetic animals, we demonstrated using diabetic model rats and confocal laser scanning microscopy that the GLP-1/GLP-1R complex was located in the endosome of diabetic islets. In addition, we showed that GLP-1 and GLP-1R co-localized with various endosomal markers and adenylate cyclase in the alpha cells of diabetic rats...
February 27, 2018: Scientific Reports
Marc Diedisheim, Masaya Oshima, Olivier Albagli, Charlotte Wennberg Huldt, Ingela Ahlstedt, Maryam Clausen, Suraj Menon, Alexander Aivazidis, Anne-Christine Andreasson, William G Haynes, Piero Marchetti, Lorella Marselli, Mathieu Armanet, Fabrice Chimienti, Raphael Scharfmann
OBJECTIVE: Dedifferentiation could explain reduced functional pancreatic β-cell mass in type 2 diabetes (T2D). METHODS: Here we model human β-cell dedifferentiation using growth factor stimulation in the human β-cell line, EndoC-βH1, and human pancreatic islets. RESULTS: Fibroblast growth factor 2 (FGF2) treatment reduced expression of β-cell markers, (INS, MAFB, SLC2A2, SLC30A8, and GCK) and activated ectopic expression of MYC, HES1, SOX9, and NEUROG3...
February 8, 2018: Molecular Metabolism
Mika Naganawa, Keunpoong Lim, Nabeel B Nabulsi, Shu-Fei Lin, David Labaree, Jim Ropchan, Kevan C Herold, Yiyun Huang, Paul Harris, Masanori Ichise, Gary W Cline, Richard E Carson
PURPOSE: Previous studies demonstrated the utility of [18 F]fluoropropyl-(+)-dihydrotetrabenazine ([18 F]FP-(+)-DTBZ) as a positron emission tomography (PET) radiotracer for the vesicular monoamine transporter type 2 (VMAT2) to quantify beta cell mass in healthy control (HC) and type 1 diabetes mellitus (T1DM) groups. Quantification of specific binding requires measurement of non-displaceable uptake. Our goal was to identify a reference tissue (renal cortex or spleen) to quantify pancreatic non-specific binding of [18 F]FP-(+)-DTBZ with the inactive enantiomer, [18 F]FP-(-)-DTBZ...
February 21, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Atsuko Masunaga, Fumihiro Ishibashi, Eitetsu Koh, Takashi Oide, Yasuo Sekine, Kenzo Hiroshima
BACKGROUND: IgG4-related disease often forms a mass and the affected lesion is clinically removed because the mass cannot be differentiated from a neoplasm. Affected lesions commonly occur in the pancreas, hepatobiliary tract, kidney, and retroperitoneum. However, the lesion rarely occurs in the thymus. A histological worldwide consensus of IgG4-related disease proposed that pathological diagnosis of IgG4-related disease should meet more than two of three major features: 1) dense lymphoplasmacytic infiltration with greater than 40% IgG4+/IgG+ plasma cells, 2) storiform fibrosis; and 3) obliterative phlebitis...
January 17, 2018: Diagnostic Pathology
Seung-Nam Jung, Hyun Sil Lim, Lihua Liu, Jae Won Chang, Young Chang Lim, Ki Sang Rha, Bon Seok Koo
Laminin subunit beta-3 (LAMB3) encodes one of the three subunits of LM-332, a protein of the extracellular matrix secreted by cultured human keratinocytes. While LAMB3 is involved in the invasive and metastatic abilities of several tumor types, including those found in the colon, pancreas, lung, cervix, stomach, and prostate, its mechanism of action in thyroid cancer has not been investigated previously. Our results show that LAMB3 is up-regulated in papillary thyroid cancer, and that its suppression reduces cell migration/invasion via down-regulation of epithelial‒mesenchymal transition-associated proteins (N-cadherin, vimentin, slug) and inhibition of matrix metalloproteinase 9...
February 9, 2018: Scientific Reports
Abraham Neelankal John, Fang-Xu Jiang
One significant health issue that plagues contemporary society is that of Type 2 diabetes (T2D). This disease is characterised by higher-than-average blood glucose levels as a result of a combination of insulin resistance and insufficient insulin secretions from the β-cells of pancreatic islets of Langerhans. Previous developmental research into the pancreas has identified how early precursor genes of pancreatic β-cells, such as Cpal, Ngn3, NeuroD, Ptf1a, and cMyc, play an essential role in the differentiation of these cells...
December 14, 2017: Journal of Diabetes and its Complications
Dawood Khan, Charlotte R Moffet, Peter R Flatt, Catriona Kelly
The endocrine pancreas is composed of islets of Langerhans, which secrete a variety of peptide hormones critical for the maintenance of glucose homeostasis. Insulin is the primary regulator of glucose and its secretion from beta-cells is tightly regulated in response to physiological demands. Direct cell-cell communication within islets is essential for glucose-induced insulin secretion. Emerging data suggest that islet connectivity is also important in the regulating the release of other islet hormones including glucagon and somatostatin...
February 2018: Peptides
Violette Coppens, Gunter Leuckx, Yves Heremans, Willem Staels, Yannick Verdonck, Luc Baeyens, Nico De Leu, Harry Heimberg
Pancreas injury by partial duct ligation (PDL) activates beta cell differentiation and proliferation in adult mouse pancreas but remains controversial regarding the anticipated increase in beta cell volume. Several reports unable to show beta cell volume augmentation in PDL pancreas used automated digital image analysis software. We hypothesized that fully automatic beta cell morphometry without manual micrograph artifact remediation introduces bias and therefore might be responsible for reported discrepancies and controversy...
2018: PloS One
Helit Cohen, Hila Barash, Irit Meivar-Levy, Kfir Molakandov, Marina Ben-Shimon, Michael Gurevich, Fatima Zoabi, Adi Har-Zahav, Rolf Gebhardt, Frank Gaunitz, Michael Gurevich, Eytan Mor, Philippe Ravassard, Shoshana Greenberger, Sarah Ferber
Transdifferentiation (TD) is the direct reprogramming of adult cells into cells of alternate fate and function. We were the first to show that liver cells can be transdifferentiated into beta-like, insulin producing cells, by ectopic expression of pancreatic transcription factors (pTFs). However, the efficiency of the process was consistently limited to <15% of the human liver cells treated in culture. The data in the current study suggest that liver to pancreas TD is restricted to a specific population of liver cells that is predisposed to undergo reprogramming...
February 2, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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