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Pancreas beta cells

Yue J Wang, Maria L Golson, Jonathan Schug, Daniel Traum, Chengyang Liu, Kumar Vivek, Craig Dorrell, Ali Naji, Alvin C Powers, Kyong-Mi Chang, Markus Grompe, Klaus H Kaestner
The human endocrine pancreas consists of multiple cell types and plays a critical role in glucose homeostasis. Here, we apply mass cytometry technology to measure all major islet hormones, proliferative markers, and readouts of signaling pathways involved in proliferation at single-cell resolution. Using this innovative technology, we simultaneously examined baseline proliferation levels of all endocrine cell types from birth through adulthood, as well as in response to the mitogen harmine. High-dimensional analysis of our marker protein expression revealed three major clusters of beta cells within individuals...
October 11, 2016: Cell Metabolism
Rehab Mohmed El-Gharbawy, Ashraf Mahmoud Emara, Sally El-Sayed Abu-Risha
The aim of this study was to use Zinc oxide nanoparticles and a standard antidiabetic drug to restore the function and structure of beta cells in a rat model of Type-2 diabetes and compare the effects of a DPP-IV inhibitor with or without zinc oxide nanoparticles (ZnONPs) using a model of type 2 diabetes (rats fed a high fat diet that was treated with a low dose of streptozotocin). Ninety male Wistar rats were randomly divided into three groups 10days after the induction of diabetes: group I: non-diabetic animals that received only the chow diet plus 2ml of 0...
October 7, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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
Mauro J Muraro, Gitanjali Dharmadhikari, Dominic Grün, Nathalie Groen, Tim Dielen, Erik Jansen, Leon van Gurp, Marten A Engelse, Francoise Carlotti, Eelco J P de Koning, Alexander van Oudenaarden
To understand organ function, it is important to have an inventory of its cell types and of their corresponding marker genes. This is a particularly challenging task for human tissues like the pancreas, because reliable markers are limited. Hence, transcriptome-wide studies are typically done on pooled islets of Langerhans, obscuring contributions from rare cell types and of potential subpopulations. To overcome this challenge, we developed an automated platform that uses FACS, robotics, and the CEL-Seq2 protocol to obtain the transcriptomes of thousands of single pancreatic cells from deceased organ donors, allowing in silico purification of all main pancreatic cell types...
September 29, 2016: Cell Systems
Ivana Nikolic, Ivana Stojanovic, Milica Vujicic, Paolo Fagone, Katia Mangano, Stanislava Stosic-Grujicic, Ferdinando Nicoletti, Tamara Saksida
Bovine colostrum is a rich source of nutrients and immunologically active components that play a role in conveying passive immunity to the offspring, protection and maturation of new-born's gastrointestinal tract. Colostrum has exerted positive effects in diseases affecting gastrointestinal tract, as well as type 2 diabetes (T2D). However, health-promoting effects in type 1 diabetes have not been reported. The aim of this study was to investigate therapeutic value of oral administration of standardized bovine colostrum derivative (SBCD) in three models of type 1 diabetes (T1D): spontaneously developed T1D in NOD mice and BB-DP rats, and in chemically induced T1D in C57BL/6 mice with multiple low doses of streptozotocin (MLDS)...
September 24, 2016: Immunobiology
Geert A Martens, Veerle De Punt, Geert Stangé
We quantified rat and human beta cell proteomes by LC-MS/MS searching for cell surface markers. In human beta cells, CD99 ranked among the plasma membrane proteins that associate a high molar abundance, to a relative degree of selectivity to the endocrine cells of the islets of Langerhans. Therefore, we investigated CD99's applicability as anchor for islet endocrine cell purification. We studied CD99 gene and protein expression by microarray, LC-MS/MS, Western blotting, flow cytometry and immunofluorescence and developed a protocol for magnetic bead-mediated beta cell enrichment from human pancreas digests using available anti-CD99 antibodies...
September 29, 2016: Journal of Tissue Engineering and Regenerative Medicine
Maayan Baron, Adrian Veres, Samuel L Wolock, Aubrey L Faust, Renaud Gaujoux, Amedeo Vetere, Jennifer Hyoje Ryu, Bridget K Wagner, Shai S Shen-Orr, Allon M Klein, Douglas A Melton, Itai Yanai
Although the function of the mammalian pancreas hinges on complex interactions of distinct cell types, gene expression profiles have primarily been described with bulk mixtures. Here we implemented a droplet-based, single-cell RNA-seq method to determine the transcriptomes of over 12,000 individual pancreatic cells from four human donors and two mouse strains. Cells could be divided into 15 clusters that matched previously characterized cell types: all endocrine cell types, including rare epsilon-cells; exocrine cell types; vascular cells; Schwann cells; quiescent and activated stellate cells; and four types of immune cells...
September 21, 2016: Cell Systems
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 beta cells. However, the role of SUMO modification in beta 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 beta cell mass...
September 20, 2016: Islets
Sayuan Liang, Karim Louchami, Hauke Kolster, Anna Jacobsen, Ying Zhang, Julian Thimm, Abdullah Sener, Joachim Thiem, Willy Malaisse, Tom Dresselaers, Uwe Himmelreich
The assessment of the β-cell mass in experimental models of diabetes and ultimately in patients is a hallmark to understand the relationship between reduced β-cell mass/function and the onset of diabetes. It has been shown before that the GLUT-2 transporter is highly expressed in both β-cells and hepatocytes and that D-mannoheptulose (DMH) has high uptake specificity for the GLUT-2 transporter. As 19-fluorine MRI has emerged as a new alternative method for MRI cell tracking because it provides potential non-invasive localization and quantification of labeled cells, the purpose of this project is to validate β-cell and pancreatic islet imaging by using fluorinated, GLUT-2 targeting mannoheptulose derivatives ((19) FMH) both in vivo and ex vivo...
September 14, 2016: Contrast Media & Molecular Imaging
Lina Zhang, Giacomo Lanzoni, Matteo Battarra, Luca Inverardi, Qibin Zhang
: The etiology of Type 1 Diabetes (T1D) remains elusive. Enzymatically isolated and cultured (EIC) islets cannot fully reflect the natural protein composition and disease process of in vivo islets, because of the stress from isolation procedures. In order to study islet protein composition in conditions close to the natural environment, we performed proteomic analysis of EIC islets, and laser capture microdissected (LCM) human islets and acinar tissue from fresh-frozen pancreas sections of three cadaveric donors...
September 13, 2016: Journal of Proteomics
Junping Wen, Ting Xue, Ying Huang, Xiaoyan Chen, Ying Xue, Wei Lin, Lizhen Zhang, Jin Yao, Huibin Huang, Jixing Liang, Liantao Li, Lixiang Lin, Lidan Shi, Liangchun Cai, Zhuangli Zhu, Gang Chen
BACKGROUND: Beta-cells in different stages have different function and capacity of proliferation, regenerative and apoptosis. We conducted this study to investigate whether there are changes in beta-cell phonotype in the development of diabetes to identify potential beta cell targets for preventing the progression of diabetes. METHODS: We conducted a cross-sectional study of pancreatic tissues obtained from 80 patients classified into three groups: 25 type2 diabetes, 25 impaired fasting glucose, and 30 non-diabetes...
September 10, 2016: Journal of Diabetes
Jiayue Yang, Richard T Waldron, Hsin-Yuan Su, Aune Moro, Hui-Hua Chang, Guido Eibl, Kevin Ferreri, Fouad R Kandeel, Aurelia Lugea, Ling Li, Stephen J Pandol
Epidemiological studies support strong links between obesity, diabetes, and pancreatic disorders including pancreatitis and pancreatic adenocarcinoma (PDAC). Type 2 diabetes (T2DM) is associated with insulin resistance, hyperglycemia, and hyperinsulinemia, the latter due to increased insulin secretion by pancreatic beta-cells. We reported that high-fat diet-induced PDAC progression in mice is associated with hyperglycemia, hyperinsulinemia, and activation of pancreatic stellate cells (PaSC). We investigated here the effects of high concentrations of insulin and glucose on mouse and human PaSC growth and fibrosing responses...
October 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Gustaf Christoffersson, Matthias G von Herrath
Cytotoxic T lymphocytes execute the killing of insulin-producing beta cells during onset of type 1 diabetes mellitus (T1D). The research community has come far in dissecting the major events in the development of this disease, but still the trigger and high-resolved information of the immunological events leading up to beta cell loss are missing. During the past decades, intravital imaging of immune responses has led to significant scientific breakthroughs in diverse models of disease, including T1D. Dynamic imaging of immune cells at the pancreatic islets during T1D onset has been made possible through the development of both advanced microscopes, and animal models that allow long-term immobilization of the pancreas...
2016: Frontiers in Immunology
Sepideh Safayee, Narges Karbalaei, Ali Noorafshan, Elham Nadimi
Thyroid hormones have important role in metabolism and impairment of glucose metabolism and insulin secretion has been shown in hypothyroid rats but the exact mechanisms for this defect are poorly understood. The aim of this study was to investigate the effect of hypothyroidism on oxidative stress parameters, insulin secretory pathway and histomorphometric changes of pancreas. In the isolated islets of the control and methimazole -treated hypothyroid insulin secretion and content, ATP production, Glucokinase, and hexokinase specific activity and kATP and L-type channels sensitivity were assayed...
August 26, 2016: European Journal of Pharmacology
Jonatan Sjölander, Elin Byman, Klaudia Kulak, Sara C Nilsson, Enming Zhang, Ulrika Krus, Gunilla T Westermark, Petter Storm, Ben C King, Erik Renström, Anna M Blom
C4b-binding protein (C4BP) is a polymer of 7 identical alpha chains and one unique beta chain synthesized in liver and pancreas. We showed previously that C4BP enhances islet amyloid polypeptide (IAPP) fibril formation in vitro. Now we report that polymeric C4BP strongly inhibited lysis of human erythrocytes incubated with monomeric IAPP while no lysis was observed after incubation with preformed IAPP fibrils. In contrast, incubation with the monomeric α-chain of C4BP was less effective. These data indicate that polymeric C4BP with multiple binding sites for IAPP enhances polymerization and neutralization of lytic activity of IAPP...
August 26, 2016: Journal of Biological Chemistry
Chen Gilor, Adam J Rudinsky, Melanie J Hall
CLINICAL RELEVANCE: Incretin-based therapies are revolutionizing the field of human diabetes mellitus (DM) by replacing insulin therapy with safer and more convenient long-acting drugs. MECHANISM OF ACTION: Incretin hormones (glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic peptide [GIP]) are secreted from the intestinal tract in response to the presence of food in the intestinal lumen. GLP-1 delays gastric emptying and increases satiety. In the pancreas, GLP-1 augments insulin secretion and suppresses glucagon secretion during hyperglycemia in a glucose-dependent manner...
September 2016: Journal of Feline Medicine and Surgery
Rodolphe Dusaulcy, Sandra Handgraaf, Svetlana Skarupelova, Florian Visentin, Christian Vesin, Mounia Heddad-Masson, Frank Reimann, Fiona Gribble, Jacques Philippe, Yvan Gosmain
Glucose homeostasis depends on the coordinated secretion of glucagon, insulin, and Glucagon-like peptide (GLP)-1 by pancreas and intestine. Obesity, which is associated with an increased risk of developing insulin resistance and type 2 diabetes, affects the function of these organs. Here, we investigate the functional and molecular adaptations of proglucagon-producing cells in obese mice to better define their involvement in type 2 diabetes development. We used GLU-Venus transgenic male mice specifically expressing Venus fluorochrome in proglucagon-producing cells...
October 2016: Endocrinology
Sonia Butalia, Gilaad G Kaplan, Bushra Khokhar, Doreen M Rabi
Type 1 diabetes is an autoimmune condition that results from the destruction of the insulin-producing beta cells of the pancreas. The excess morbidity and mortality resulting from its complications, coupled with its increasing incidence, emphasize the importance of better understanding the causes of this condition. Over the past several decades, a substantive amount of work has been done and, although many advances have occurred in identifying disease-susceptibility genes, there has been a lag in understanding the environmental triggers...
August 18, 2016: Canadian Journal of Diabetes
S Ueberberg, H Jütte, W Uhl, W E Schmidt, M A Nauck, E Montanya, A Tannapfel, J J Meier
AIMS/HYPOTHESIS: Incretin-based therapies have been associated with an increased risk of pancreatitis. Recently, various histological abnormalities have been reported in human pancreatic tissue from brain-dead organ donors that had been exposed to incretin-based drugs. In the present study we examined pancreatic tissue collected at surgery. METHODS: Human pancreatic tissue from seven type 2-diabetic patients treated with incretin-based drugs (type 2-I), six diabetic patients without incretin treatment (type 2-NI), eleven patients without diabetes (no diabetes) and nine brain-dead organ donors (BDOD) was examined...
August 22, 2016: Diabetes, Obesity & Metabolism
Inge van der Kroon, Lieke Joosten, Berthold A Nock, Theodosia Maina, Otto C Boerman, Maarten Brom, Martin Gotthardt
OBJECTIVE: Accurate assessment of the (111)In-exendin-3 uptake within the pancreas requires exact delineation of the pancreas, which is highly challenging by MRI and CT in rodents. In this study, the pancreatic tracer (99m)Tc-demobesin-4 was evaluated for accurate delineation of the pancreas to be able to accurately quantify (111)In-exendin-3 uptake within the pancreas. METHODS: Healthy and alloxan-induced diabetic Brown Norway rats were injected with the pancreatic tracer (99m)Tc-demobesin-4 ([(99m)Tc-N4-Pro(1),Tyr(4),Nle(14)]bombesin) and the beta cell tracer (111)In-exendin-3 ([(111)In-DTPA-Lys(40)]exendin-3)...
October 3, 2016: Molecular Pharmaceutics
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