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Pancreatic islets

Jing-Woei Li, Heung-Man Lee, Ying Wang, Amy Hin-Yan Tong, Kevin Y Yip, Stephen Kwok-Wing Tsui, Si Lok, Risa Ozaki, Andrea O Luk, Alice P S Kong, Wing-Yee So, Ronald C W Ma, Juliana C N Chan, Ting-Fung Chan
Protein interactions play significant roles in complex diseases. We analyzed peripheral blood mononuclear cells (PBMC) transcriptome using a multi-method strategy. We constructed a tissue-specific interactome (T2Di) and identified 420 molecular signatures associated with T2D-related comorbidity and symptoms, mainly implicated in inflammation, adipogenesis, protein phosphorylation and hormonal secretion. Apart from explaining the residual associations within the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) study, the T2Di signatures were enriched in pathogenic cell type-specific regulatory elements related to fetal development, immunity and expression quantitative trait loci (eQTL)...
October 18, 2016: Scientific Reports
Chafiq Hamdouchi, Steven D Kahl, Anjana Patel Lewis, Guemalli R Cardona, Richard W Zink, Keyue Chen, Thomas E Eessalu, James V Ficorilli, Marialuisa C Marcelo, Keith A Otto, Kelly L Wilbur, Jayana P Lineswala, Jared L Piper, D Scott Coffey, Stephanie A Sweetana, Joseph V Haas, Dawn A Brooks, Edward J Pratt, Ruth M Belin, Mark A Deeg, Xiaosu Ma, Ellen A Cannady, Jason T Johnson, Nathan P Yumibe, Qi Chen, Pranab Maiti, Chahrzad Montrose-Rafizadeh, Yanyun Chen, Anne Reifel Miller
The G protein-coupled receptor 40 (GPR40) also known as Free Fatty Acid Receptor 1 (FFAR1) is highly expressed in pancreatic, islet cells and responds to endogenous fatty acids resulting in amplification of insulin secretion only in the presence of elevated glucose levels. Hypothesis driven structural modifications to endogenous FFAs, focused on breaking planarity and reducing lipophilicity, led to the identification of spiropiperidine and tetrahydroquinoline acid derivatives as GPR40 agonists with unique pharmacology, selectivity and pharmacokinetic properties...
October 17, 2016: Journal of Medicinal Chemistry
Maryam Kaviani, Negar Azarpira, Mohammad Hossein Karimi, Ismail Al-Abdullah
Cell-based therapies suggest novel treatments to overcome the complication of the current therapeutic approaches in diabetes mellitus type 1. Replacement of the destroyed pancreatic islet β-cells by appropriate alternative cells needs an efficient approach to differentiate the cells into viable and functional insulin producing cells. Small non-coding RNA molecules, MicroRNAs (miRNA), have critical roles in post-transcriptional regulation of gene expression. Therefore, they can direct the cells toward β-cell like cells and control islet β-cell development...
October 15, 2016: Cell Biology International
Roi Isaac, Ido Goldstein, Noa Furth, Neta Zilber, Sarina Streim, Sigalit Boura-Halfon, Eytan Elhanany, Varda Rotter, Moshe Oren, Yehiel Zick
Earlier reported small interfering RNA (siRNA) high-throughput screens, identified seven-transmembrane superfamily member 3 (TM7SF3) as a novel inhibitor of pancreatic β-cell death. Here we show that TM7SF3 maintains protein homeostasis and promotes cell survival through attenuation of ER stress. Overexpression of TM7SF3 inhibits caspase 3/7 activation. In contrast, siRNA-mediated silencing of TM7SF3 accelerates ER stress and activation of the unfolded protein response (UPR). This involves inhibitory phosphorylation of eukaryotic translation initiation factor 2α activity and increased expression of activating transcription factor-3 (ATF3), ATF4 and C/EBP homologous protein, followed by induction of apoptosis...
October 14, 2016: Cell Death and Differentiation
J Ciriza, L Saenz Del Burgo, R M Hernández, G Orive, J L Pedraz
Alginate cell microencapsulation implies the immobilization of cells within a polymeric membrane that allows the bidirectional diffusion of nutrients and oxygen inside the microcapsules and the release of waste and therapeutic molecules outside them. This technology has been applied to several cell types and it has been extensively described with pancreatic islets. However, other cells such as myoblasts are being currently studied and showing high interest. Moreover, different systems and approaches have been developed for cell encapsulation such as electrostatic extrusion and Flow focusing technology...
2017: Methods in Molecular Biology
Kevin Enck, John Patrick McQuilling, Giuseppe Orlando, Riccardo Tamburrini, Sittadjody Sivanandane, Emmanuel C Opara
Islet transplantation (IT) has recently been shown to be a promising alternative to pancreas transplantation for reversing diabetes. IT requires the isolation of the islets from the pancreas, and these islets can be used to fabricate a bio-artificial pancreas. Enzymatic digestion is the current gold standard procedure for islet isolation but has lingering concerns. One such concern is that it has been shown to damage the islets due to nonselective tissue digestion. This chapter provides a detailed description of a nonenzymatic method that we are exploring in our lab as an alternative to current enzymatic digestion procedures for islet isolation from human and nonhuman pancreatic tissues...
2017: Methods in Molecular Biology
William F Kendall, Emmanuel C Opara
Since the discovery of insulin by Banting and Best in 1921, the prognosis and treatment options for individuals with diabetes have improved. The development of various insulin types, various oral agents, and insulin pumps have improved the available medical options for individuals afflicted with diabetes. The current need for frequent blood glucose monitoring imposed by multiple daily insulin injections, result in significant life-style challenges for in individuals afflicted with Type 1 diabetes (T1D). In contrast the use of surgical interventions, such as whole organ pancreas transplantation (PT) requires less-intensive glucose monitoring while the organ is viable...
2017: Methods in Molecular Biology
John Patrick McQuilling, Emmanuel C Opara
A major obstacle to long-term performance of tissue construct implants in regenerative medicine is the inherent hypoxia to which cells in the engineered construct are exposed prior to vascularization of the implant. Various approaches are currently being designed to address this problem. An emerging area of interest on this issue is the use of peroxide-based materials to generate oxygen during the critical period of extended hypoxia that occurs from the time cells are in culture waiting to be used in tissue engineering devices through the immediate post-implant period...
2017: Methods in Molecular Biology
Marcus D Darabbie, Emmanuel C Opara
The promise of pancreatic islet transplantation is hindered by organ shortage, and the need for immunosuppression of transplant recipient in order to prevent rejection. Alginate microencapsulation can overcome these hurdles; however further optimization of this technique is required. Among the critical factors to be optimized is the durability of alginate microcapsules, which can be determined by their mechanical strength tests. Here we describe several simple and reliable methods to assist in assessing the mechanical strength of alginate beads...
2017: Methods in Molecular Biology
William F Kendall, Emmanuel C Opara
Application of microencapsulation to the immunoisolation of pancreatic islets holds promise for expanding the use of islet transplantation as a treatment option for Type 1 diabetes. It is generally believed that successful development of a reliable methodology will ideally allow for transplantation of pancreatic islets that are protected from the immune system, thereby obviating the need for the use of immunosuppressive drugs and their attendant side effects. In addition, this technology has the potential to expand the donor pool as islets from nonhuman donors could be used as xenografts in human patients...
2017: Methods in Molecular Biology
Varna Sharma, Michael Hunckler, Melur K Ramasubramanian, Emmanuel C Opara, Kalyan C Katuri
Bioartificial pancreas made of insulin-secreting islets cells holds great promise in the treatment of individuals with Type-1 diabetes. Successful islet cell microencapsulation in biopolymers is a key step for providing immunoisolation of transplanted islet cells. Because of the variability in the size and shape of pancreatic islets, one of the main obstacles in their microencapsulation is the inability to consistently control shape, size, and microstructure of the encapsulating biopolymer capsule. In this chapter, we provide a detailed description of a microfluidic approach to islet cell encapsulation in alginate that might address the microencapsulation challenges...
2017: Methods in Molecular Biology
Fabio Arturo Grieco, Guido Sebastiani, Jonas Juan-Mateu, Olatz Villate, Laura Marroqui, Laurence Ladrière, Ksenya Tugay, Romano Regazzi, Marco Bugliani, Piero Marchetti, Francesco Dotta, Décio L Eizirik
Type 1 Diabetes is an autoimmune disease leading to beta cell destruction. MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression and organ formation. They participate in the pathogenesis of several autoimmune diseases, but the nature of miRNAs contributing to beta cell death in T1D and their target genes remain to be clarified.We performed a miRNA expression profile on human islet preparations exposed to the cytokines IL-1β+IFN-γ. Confirmation of miRNAs and target genes modification in human beta cells was performed by real-time qPCR...
October 13, 2016: Diabetes
Y Kaneko, N Onda, Y Watanabe, M Shibutani
5-Hydroxytryptamine (5-HT) produced by enterochromaffin (EC) cells is an important enteric mucosal signaling ligand and has been implicated in several gastrointestinal diseases, including inflammatory bowel disease and functional disorders such as irritable bowel syndrome. The present study reports a new, simple and rapid visualization method of 5-HT-producing EC cells utilizing detection of autofluorescence in paraffin-embedded tissue sections after formalin fixation. In human samples, there was a high incidence of autofluorescence+ cells in the 5-HT+ cells in the pyloric, small intestinal and colonic glands, while co-localization was lacking between autofluorescence+ and gastrin+ cells in the pyloric and small intestinal glands...
September 29, 2016: European Journal of Histochemistry: EJH
Rashmi B Prasad, Leif Groop
RNA sequencing of human pancreatic islets has provided important insights into the islet transcriptome but little information on the specific cells. In this issue, Segerstolpe et al. (2016) and Xin et al. (2016b) report on the transcriptome of single pancreatic cells from non-diabetic and type 2 diabetic donors.
October 11, 2016: Cell Metabolism
Youngjin Kim, Hyeongseok Kim, Ung Hyun Ko, Youjin Oh, Ajin Lim, Jong-Woo Sohn, Jennifer H Shin, Hail Kim, Yong-Mahn Han
Insulin secretion is elaborately modulated in pancreatic ß cells within islets of three-dimensional (3D) structures. Using human pluripotent stem cells (hPSCs) to develop islet-like structures with insulin-producing ß cells for the treatment of diabetes is challenging. Here, we report that pancreatic islet-like clusters derived from hESCs are functionally capable of glucose-responsive insulin secretion as well as therapeutic effects. Pancreatic hormone-expressing endocrine cells (ECs) were differentiated from hESCs using a step-wise protocol...
October 12, 2016: Scientific Reports
Adam Neal, Austin Rountree, Kelly Kernan, Brian Van Yserloo, Huiliang Zhang, Benjamin J Reed, William Osborne, Wang Wang, Ian R Sweet
A real time method to measure intracellular H2O2 would be very impactful in characterizing rapid changes that occur in physiologic and pathophysiologic states. Current methods do not provide the sensitivity, specificity and spatiotemporal resolution needed for such experiments on intact cells. We developed the use of HyPer, a genetic indicator for H2O2 that can be expressed in the cytosol (cyto-HyPer) or the mitochondria (mito-HyPer) of live cells. INS-1 cells or islets were permeabilized and the cytosolic HyPer signal was a linear function of extracellular H2O2, allowing fluorescent cyto-HyPer signals to be converted to H2O2 concentrations...
October 11, 2016: Biochemical Journal
Junbi Xv, Qianwen Ming, Xiaotong Wang, Wenjing Zhang, Zheng Li, Shuai Wang, Yulin Li, Lisha Li
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by lack of insulin and irreversible destruction of islet β cells. In order to alleviate the symptoms, lifelong exogenous insulin administration has been the primary treatment of T1DM. In recent years, as a novel promising therapy, the transplantation of mesenchymal stem cells (MSCs) with or without pancreatic islets has achieved great therapeutic effects in animal models due to their multipotency along with their secretion of cytokines, angiogenic factors and immunomodulatory substances...
October 10, 2016: Cell and Tissue Research
Junfeng Li, Johann Karunananthan, Bradley Pelham, Fouad Kandeel
It was estimated that every year more than 30000 persons in the United States - approximately 80 people per day - are diagnosed with type 1 diabetes (T1D). T1D is caused by autoimmune destruction of the pancreatic islet (β cells) cells. Islet transplantation has become a promising therapy option for T1D patients, while the lack of suitable tools is difficult to directly evaluate of the viability of the grafted islet over time. Positron emission tomography (PET) as an important non-invasive methodology providing high sensitivity and good resolution, is able to accurate detection of the disturbed biochemical processes and physiological abnormality in living organism...
September 28, 2016: World Journal of Radiology
Diego Soares Carvalho, Marilia Melo Diniz, André Abour Haidar, Maria de Fátima Cavanal, Eduardo da Silva Alves, Angelo Rafael Carpinelli, Frida Zaladek Gil, Aparecida Emiko Hirata
Maternal hyperglycemia can result in defects in glucose metabolism and pancreatic β-cell function in offspring. The purpose of this study was to evaluate the impact of maternal diabetes mellitus on pancreatic islets, muscle and adipose tissue of the offspring, with or without oral l-Arginine supplementation. The induction of diabetes was performed using streptozotocin (60mg/kg). Animals were studied at 3 months of age and treatment (sucrose or l-Arginine) was administered from weaning. We observed that l-Arg improved insulin sensitivity in the offspring of diabetic mothers (DA), reflected by higher insulin-induced phosphorylation of Akt in muscle and adipose tissue...
October 4, 2016: European Journal of Pharmacology
Yi-Jen Liao, Tzong-Shyuan Lee, Yuh-Ching Twu, Shih-Ming Hsu, Ching-Ping Yang, Chung-Kwe Wang, Yu-Chih Liang, Yi-Ming Arthur Chen
BACKGROUND: Glycine N-methyltransferase (GNMT) is abundantly expressed in the normal liver but is down-regulated in liver cancer tissues. GNMT knockout (Gnmt-/-) mice can spontaneously develop chronic hepatitis, fatty liver, and liver cancer. We previously demonstrated that hepatic GNMT is decreased in high-fat-diet-induced type 2 diabetes mellitus, but its contribution to metabolic syndrome is unclear. Here we show that GNMT modulates key aspects of metabolic syndrome in mice. METHODS: Eleven-week-old Gnmt-/- and wild-type (WT) mice with a C57BL/6 genetic background were used in this study...
October 4, 2016: Journal of Biomedical Science
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