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Pancreatic islet

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https://www.readbyqxmd.com/read/28525638/glucokinase-gene-may-be-a-more-suitable-target-than-the-insulin-gene-for-detection-of-beta-cell-death
#1
J Sklenarova, L Petruzelkova, S Kolouskova, J Lebl, Z Sumnik, O Cinek
Detection and quantification of unmethylated circulating insulin (INS) DNA presumably released from beta cells has been previously used for assessing their destruction. As the targets within the INS gene suffer from suboptimal specificity, we sought to improve the assay parameters by using the glucokinase gene (GCK) tissue-specific pancreatic promoter.The amount of methylated and unmethylated GCK DNA was measured using a droplet PCR assay, and compared with the previously published INS-targeted assay. The method was tested using synthetic target sequences and DNA from pancreatic islets, blood, brain, kidney, large intestine, liver, lung, small intestine and stomach...
May 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28523592/islet-microencapsulation-strategies-and-clinical-status-in-diabetes
#2
REVIEW
Mustafa Omami, James J McGarrigle, Mick Reedy, Douglas Isa, Sofia Ghani, Enza Marchese, Matthew A Bochenek, Maha Longi, Yuan Xing, Ira Joshi, Yong Wang, José Oberholzer
PURPOSE OF REVIEW: Type 1 diabetes mellitus (T1DM) is an autoimmune disease that results from the destruction of insulin-producing pancreatic β cells in the islets of Langerhans. Islet cell transplantation has become a successful therapy for specific patients with T1DM with hypoglycemic unawareness. The reversal of T1DM by islet transplantation is now performed at many major medical facilities throughout the world. However, many challenges must still be overcome in order to achieve continuous, long-term successful transplant outcomes...
July 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28522407/high-throughput-screening-and-bioinformatic-analysis-to-ascertain-compounds-that-prevent-saturated-fatty-acid-induced-%C3%AE-cell-apoptosis
#3
Seung-Hee Lee, Daniel Cunha, Carlo Piermarocchi, Giovanni Paternostro, Anthony Pinkerton, Laurence Ladriere, Piero Marchetti, Decio L Eizirik, Miriam Cnop, Fred Levine
Pancreatic β-cell lipotoxicity is a central feature of the pathogenesis of type 2 diabetes. To study the mechanism by which fatty acids cause β-cell death and develop novel approaches to prevent it, a high-throughput screen on the β-cell line INS1 was carried out. The cells were exposed to palmitate to induce cell death and compounds that reversed palmitate-induced cytotoxicity were ascertained. Hits from the screen were analyzed by an increasingly more stringent testing funnel, ending with studies on primary human islets treated with palmitate...
May 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28515766/pancreatic-protective-and-hypoglycemic-effects-of-vitex-agnus-castus-l-fruit-hydroalcoholic-extract-in-d-galactose-induced-aging-mouse-model
#4
Akram Ahangarpour, Ali Akbar Oroojan, Layasadat Khorsandi, Seyedeh Asma Najimi
D-galactose induces pancreatic disorder along with aging mouse model. Vitex agnus-castus (VAC) has potential pancreatic protective effect. Hence, this study was designed to evaluate the hypoglycemic and pancreas protective effects of VAC hydroalcoholic extract in D-galactose-induced aging female mice. In the present experimental study, 72 adult female Naval Medical Research Institute (NMRI) mice (weighing 30-35 g) were divided into 6 groups of control, VAC hydroalcoholic extract, D-galactose, D-galactose + VAC hydroalcoholic extract, aged, aged + VAC hydroalcoholic extract...
April 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28512677/heterogeneity-of-proliferative-markers-in-pancreatic-%C3%AE-cells-of-patients-with-severe-hypoglycemia-following-roux-en-y-gastric-bypass
#5
Mary-Elizabeth Patti, Allison B Goldfine, Jiang Hu, Dag Hoem, Anders Molven, Jeffrey Goldsmith, Wayne H Schwesinger, Stefano La Rosa, Franco Folli, Rohit N Kulkarni
AIMS: Severe postprandial hypoglycemia with neuroglycopenia is an increasingly recognized, debilitating complication of Roux-en-Y gastric bypass (RYGB) surgery. Increased secretion of insulin and incretin hormones is implicated in its pathogenesis. Histopathologic examination of pancreas has demonstrated increased islet size and/or nuclear diameter in post-RYGB patients who underwent pancreatectomy for severe refractory hypoglycemia with neuroglycopenia (RYGB + NG). We aimed to determine whether β-cell proliferation or apoptosis is altered in RYGB + NG...
May 17, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28512156/effects-of-metformin-on-compensatory-pancreatic-%C3%AE-cell-hyperplasia-in-mice-fed-a-high-fat-diet
#6
Kazuki Tajima, Jun Shirakawa, Tomoko Okuyama, Mayu Kyohara, Shunsuke Yamazaki, Yu Togashi, Yasuo Terauchi
Metformin has been widely used for the treatment of type 2 diabetes. However, the effect of metformin on pancreatic β-cells remains controversial. In this study, we investigated the impacts of treatment with metformin on pancreatic β-cells in a mouse model fed a high-fat diet (HFD), which triggers adaptive β-cell replication. An 8-week treatment with metformin improved insulin resistance and suppressed the compensatory β-cell hyperplasia induced by HFD-feeding. In contrast, the increment in β-cell mass arising from 60 weeks of HFD-feeding was similar in mice treated with and those treated without metformin...
May 16, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28510792/a-systematic-review-of-proinsulin-secreting-pancreatic-neuroendocrine-tumors
#7
Timothy D Murtha, Beatrice C Lupsa, Sachin Majumdar, Dhanpat Jain, Ronald R Salem
BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are a heterogeneous group of islet cell-derived neoplasms with a propensity toward hormone production. Among PNETs, proinsulin-secreting tumors (proinsulinomas) are exceedingly rare. The objective of this study is to collect and summarize the existing literature to provide a comprehensive evaluation of this uncommon disease. METHODS: A systematic review was performed to characterize the clinicopathologic features of proinsulinoma...
May 16, 2017: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/28510423/phycocyanin-functionalized-selenium-nanoparticles-reverse-palmitic-acid-induced-pancreatic-beta-cells-apoptosis-by-enhancing-cellular-uptake-and-blocking-ros-mediated-mitochondria-dysfunction
#8
Chang Liu, Yuanting Fu, Chang-E Li, Tianfeng Chen, Xiaoling Li
Accumulation of palmitic acid (PA) in human bodies could cause damage to pancreatic beta cells and lead to chronic diseases by generation of reactive oxygen species (ROS). Therefore, it is of great significance to search for nutrition available agents with antioxidant activity to protect pancreatic islet cells against PA-induced damage. Phycocyanin (PC) and selenium (Se) have been reported to have excellent antioxidant activity. In this study, PC-functionalized selenium nanoparticles (PC-SeNPs) were synthesized to investigate the in vitro protective effects on INS-1E rat insulinoma beta cells against PA-induced cell death...
May 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28510280/modelling-the-iatrogenic-pancreatic-cancer-risk-after-islet-autotransplantation-in-mouse
#9
E Dugnani, V Pasquale, D Liberati, A Citro, E Cantarelli, S Pellegrini, P Marra, T Canu, G Balzano, M Scavini, A Esposito, C Doglioni, L Piemonti
Iatrogenic pancreatic cancer metastasis after islet infusion is a potential risk of islet autotransplantation performed after pancreatectomy. To model this risk islets and/or pancreatic exocrine clusters obtained from a genetically engineered mouse model for pancreatic ductal adenocarcinoma (the LSL-Kras(G12D/+) ;LSL-Trp53(R172H/+) ;Pdx-1-Cre, termed KPC mouse) were transplanted via the portal vein in syngeneic wild type (WT) severely diabetic recipients in the following treatment groups: group A (n=11) received KPC exocrine clusters in volume equal to 250 equivalent islets (IEQs); group B (n=12) received 250 WT IEQs mixed with KPC exocrine clusters (1:1 volume ratio); group C (n=5) received 250 KPC IEQs and group D (n=7) received 250 wild type IEQs...
May 16, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28509692/t1d-autoantibodies-room-for-improvement
#10
Liping Yu, Zhiyuan Zhao, Andrea K Steck
PURPOSE OF REVIEW: Type 1 diabetes (T1D) is now predictable by measuring major islet autoantibodies (IAbs) against insulin and other pancreatic β cells proteins including GAD65 (GADA), islet antigen 2 (IA-2A), and zinc transporter 8 (ZnT8A). The assay technology for IAbs has made great progress; however, several important aspects still need to be addressed and improved. RECENT FINDINGS: Currently a radio-binding assay has been well established as the 'gold' standard assay for all four IAbs...
May 13, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28508555/laminin-and-collagen-iv-inclusion-in-immunoisolating-microcapsules-reduces-cytokine-mediated-cell-death-in-human-pancreatic-islets
#11
Alberto Llacua, Bart J de Haan, Paul de Vos
Extracellular matrix (ECM) molecules have several functions in pancreatic islets including provision of mechanical support and prevention of cytotoxicity during inflammation. During islet isolation, ECM-connections are damaged and are not restored after encapsulation and transplantation. Inclusion of specific combinations of collagen type IV and laminins in immunoisolating capsules can enhance survival of pancreatic islets. Here we investigated whether ECM can also enhance survival and lower susceptibility of human islets to cytokine-mediated cytotoxicity...
May 16, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28507914/intra-islet-endothelial-cell-and-%C3%AE-cell-crosstalk-implication-for-islet-cell-transplantation
#12
REVIEW
Siddharth Narayanan, Gopalakrishnan Loganathan, Maheswaran Dhanasekaran, William Tucker, Ankit Patel, Venugopal Subhashree, SriPrakash Mokshagundam, Michael G Hughes, Stuart K Williams, Appakalai N Balamurugan
The intra-islet microvasculature is a critical interface between the blood and islet endocrine cells governing a number of cellular and pathophysiological processes associated with the pancreatic tissue. A growing body of evidence indicates a strong functional and physical interdependency of β-cells with endothelial cells (ECs), the building blocks of islet microvasculature. Intra-islet ECs, actively regulate vascular permeability and appear to play a role in fine-tuning blood glucose sensing and regulation...
April 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28507444/antibodies-against-glutamic-acid-decarboxylase-and-indices-of-insulin-resistance-and-insulin-secretion-in-nondiabetic-adults-a-cross-sectional-study
#13
Carlos O Mendivil, Freddy Jk Toloza, Maria L Ricardo-Silgado, Martha C Morales-Álvarez, Jose O Mantilla-Rivas, Jairo A Pinzón-Cortés, Hernán N Lemus
BACKGROUND: Autoimmunity against insulin-producing beta cells from pancreatic islets is a common phenomenon in type 1 diabetes and latent autoimmune diabetes in adults. Some reports have also related beta-cell autoimmunity to insulin resistance (IR) in type 2 diabetes. However, the extent to which autoimmunity against components of beta cells is present and relates to IR and insulin secretion in nondiabetic adults is uncertain. AIM: To explore the association between antibodies against glutamic acid decarboxylase (GADA), a major antigen from beta cells, and indices of whole-body IR and beta-cell capacity/insulin secretion in adults who do not have diabetes...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28505316/pancreas-atrophy-and-islet-amyloid-deposition-in-patients-with-elderly-onset-type-2-diabetes
#14
An Xin, Hiroki Mizukami, Wataru Inaba, Taro Yoshida, Yu-Ki Takeuchi, Soroku Yagihashi
Context: With prolonged life-expectancy, we often encounter patients with elderly onset type 2 diabetes (eT2DM). Although clinical features of eT2DM are suggested to be different from those in patients with middle-aged onset type 2 diabetes (mT2DM), islet pathology in eT2DM has not been addressed. Objective: We attempted to characterize the pancreatic pathology in eT2DM and sought for its clinical implication. Methods: Pancreata from 13 young non-diabetic (20-29 y...
May 12, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28504618/butyrate-reduces-high-fat-diet-induced-metabolic-alterations-hepatic-steatosis-and-pancreatic-beta-cell-and-intestinal-barrier-dysfunctions-in-prediabetic-mice
#15
V A Matheus, Lcs Monteiro, R B Oliveira, D A Maschio, C B Collares-Buzato
In this study, we investigated the effect of diet supplementation with sodium butyrate (5% w/w), a short-chain fatty acid produced by the intestinal microbiota, on metabolic parameters, body adiposity, hepatic and pancreatic lipid accumulation, beta cell function/mass as well as on the structure and function of the tight junction-mediated intestinal epithelial barrier in both normal and obese/prediabetic C57 mice fed a regular (control) or high-fat diet for 60 days, respectively. Butyrate treatment significantly inhibited all the high-fat-induced metabolic dysfunctions evaluated, i...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28502980/w2476-ameliorates-%C3%AE-cell-dysfunction-and-exerts-therapeutic-effects-in-mouse-models-of-diabetes-via-modulation-of-the-thioredoxin-interacting-protein-signaling-pathway
#16
Ting Li, Guang-Yao Lin, Li Zhong, Yan Zhou, Jia Wang, Yue Zhu, Yang Feng, Xiao-Qing Cai, Qing Liu, Olivier Nosjean, Jean A Boutin, Pierre Renard, De-Hua Yang, Ming-Wei Wang
Recent evidence shows that high glucose levels recruit carbohydrate response element-binding protein, which binds the promoter of thioredoxin-interacting protein (txnip), thereby regulating its expression in β-cells. Overexpression of txnip not only induces β-cell apoptosis but also reduces insulin production. Thus, the discovery of compounds that either inhibit TXNIP activity or suppress its expression was the focus of the present study. INS-1E cells stably transfected with either a txnip proximal glucose response element connected to a luciferase reporter plasmid (BG73) or full-length txnip promoter connected to a luciferase reporter plasmid (CL108) were used in primary and secondary high-throughput screening campaigns, respectively...
May 15, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28500395/the-human-serum-protein-c4b-binding-protein-inhibits-pancreatic-iapp-induced-inflammasome-activation
#17
Klaudia Kulak, Gunilla T Westermark, Nikolina Papac-Milicevic, Erik Renström, Anna M Blom, Ben C King
AIMS/HYPOTHESIS: Inflammasome activation and subsequent IL-1β production is a driver of islet pathology in type 2 diabetes. Oligomers, but not mature amyloid fibrils, of human islet amyloid polypeptide (IAPP), which is co-secreted with insulin, trigger NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome activation. C4b-binding protein (C4BP), present in serum, binds to IAPP and affects transition of IAPP monomers and oligomers to amyloid fibrils. We therefore hypothesised that C4BP inhibits IAPP-mediated inflammasome activation and IL-1β production...
May 12, 2017: Diabetologia
https://www.readbyqxmd.com/read/28499695/dapagliflozin-modulates-glucagon-secretion-in-an-sglt2-independent-manner-in-murine-alpha-cells
#18
A Solini, G Sebastiani, L Nigi, E Santini, C Rossi, F Dotta
AIM: SGLT2 inhibitors reduce renal glucose uptake through an insulin-independent mechanism. They also increase glucagon concentration, although the extent to which this is due to a direct effect on pancreatic alpha cells remains unclear. METHODS: In the present work, αTC1 cells treated with the SGLT2 inhibitor dapagliflozin (Dapa) were analyzed for glucose transporters, molecular mediators of hormone secretion, glucagon and GLP-1 release, and the effects of somatostatin...
May 9, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28497293/calcium-oscillation-frequency-sensitive-gene-regulation-and-homeostatic-compensation-in-pancreatic-formula-see-text-cells
#19
Vehpi Yildirim, Richard Bertram
Pancreatic islet [Formula: see text]-cells are electrically excitable cells that secrete insulin in an oscillatory fashion when the blood glucose concentration is at a stimulatory level. Insulin oscillations are the result of cytosolic [Formula: see text] oscillations that accompany bursting electrical activity of [Formula: see text]-cells and are physiologically important. ATP-sensitive [Formula: see text] channels (K(ATP) channels) play the key role in setting the overall activity of the cell and in driving bursting, by coupling cell metabolism to the membrane potential...
May 11, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28496181/the-neuronal-k-cl-co-transporter-2-slc12a5-modulates-insulin-secretion
#20
Shams Kursan, Timothy S McMillen, Pavani Beesetty, Eduardo Dias-Junior, Mohammed M Almutairi, Abu A Sajib, J Ashot Kozak, Lydia Aguilar-Bryan, Mauricio Di Fulvio
Intracellular chloride concentration ([Cl(-)]i) in pancreatic β-cells is kept above electrochemical equilibrium due to the predominant functional presence of Cl(-) loaders such as the Na(+)K(+)2Cl(-) co-transporter 1 (Slc12a2) over Cl(-)extruders of unidentified nature. Using molecular cloning, RT-PCR, Western blotting, immunolocalization and in vitro functional assays, we establish that the "neuron-specific" K(+)Cl(-) co-transporter 2 (KCC2, Slc12a5) is expressed in several endocrine cells of the pancreatic islet, including glucagon secreting α-cells, but particularly in insulin-secreting β-cells, where we provide evidence for its role in the insulin secretory response...
May 11, 2017: Scientific Reports
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