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pancreatic diabetes

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https://www.readbyqxmd.com/read/28213757/germinal-centre-frequency-is-decreased-in-pancreatic-lymph-nodes-from-individuals-with-recent-onset-type-1-diabetes
#1
Abby Willcox, Sarah J Richardson, Lucy S K Walker, Sally C Kent, Noel G Morgan, Kathleen M Gillespie
AIMS/HYPOTHESIS: Pancreatic lymph nodes (PLNs) are critical sites for the initial interaction between islet autoantigens and autoreactive lymphocytes, but the histology of PLNs in tissue from individuals with type 1 diabetes has not been analysed in detail. The aim of this study was to examine PLN tissue sections from healthy donors compared with those at risk of, or with recent-onset and longer-duration type 1 diabetes. METHODS: Immunofluorescence staining was used to examine PLN sections from the following donor groups: non-diabetic (n=15), non-diabetic islet autoantibody-positive (n=5), recent-onset (≤1...
February 17, 2017: Diabetologia
https://www.readbyqxmd.com/read/28213664/type-2-diabetes-remission-after-roux-en-y-gastric-bypass-evidence-for-increased-expression-of-jejunal-genes-encoding-regenerating-pancreatic-islet-derived-proteins-as-a-potential-mechanism
#2
Priscila Sala, Raquel Susana Torrinhas, Danielle Cristina Fonseca, Steven Heymsfield, Daniel Giannella-Neto, Dan Linetzky Waitzberg
BACKGROUND: Intestinal expression of regenerating pancreatic islet-derived protein-encoding genes (REG) would be enhanced after Roux-en-Y gastric bypass (RYGB) and would affect postoperative type 2 diabetes remission (T2Dr). METHODS: Intestinal biopsy samples were collected from 20 adult obese women with T2D before and 3 months after RYGB. Levels of REG expression and the gene encoding its putative receptor (EXTL3) were assessed by microarray and validated by quantitative RT-PCR...
February 17, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28213644/circulating-micrornas-and-diabetes-mellitus-a-novel-tool-for-disease-prediction-diagnosis-and-staging
#3
REVIEW
G Sebastiani, L Nigi, G E Grieco, F Mancarella, G Ventriglia, F Dotta
Diabetes is a complex, multifactorial group of metabolic diseases characterized by chronic hyperglycaemia due to pancreatic beta-cell dysfunction and/or loss. It is characterized by an asymptomatic and highly variable prodromic phase, which renders diabetes mellitus difficult to be predicted with sufficient accuracy. Despite several efforts in the identification and standardization of newly trustable. Biomarkers able to predict and follow-up diabetes and to specifically subtype its different forms, few of them have proven of clinical utility...
February 17, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28213324/qing-hua-granule-induces-glp-1-secretion-via-bitter-taste-receptor-in-db-db-mice
#4
Junyan Li, Jie Xu, Ruifang Hou, Xin Jin, Jingyi Wang, Na Yang, Li Yang, Li Liu, Feng Tao, Hao Lu
Qing-Hua Granule (QHG), the modified formulation of a classical Chinese prescription named Gegen Qinlian Decoction, was clinically employed to treat type 2 diabetes mellitus (T2DM) through regulation of glucagon-like peptide-1 (GLP-1). However, the potential mechanism is unknown. We investigate whether QHG induces GLP-1 secretion via activation of bitter taste receptor (TAS2R) pathway in the gastrointestinal tract of db/db mice. The db/db mice were intragastrically (i.g.) administered QHG (low/medium/high dose) once daily for 8 weeks...
February 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28212332/type-1-diabetes-candidate-genes-linked-to-pancreatic-islet-cell-inflammation-and-beta-cell-apoptosis
#5
REVIEW
Joachim Størling, Flemming Pociot
Type 1 diabetes (T1D) is a chronic immune-mediated disease resulting from the selective destruction of the insulin-producing pancreatic islet β-cells. Susceptibility to the disease is the result of complex interactions between environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established...
February 16, 2017: Genes
https://www.readbyqxmd.com/read/28211608/preclinical-characterisation-of-55p0251-a-novel-compound-that-amplifies-glucose-stimulated-insulin-secretion-and-counteracts-hyperglycaemia-in-rodents
#6
Karin Stadlbauer, Barbara Brunmair, Zsuzsanna Lehner, Immanuel Adorjan, Thomas Scherer, Anton Luger, Leonhardt Bauer, Clemens Fürnsinn
AIMS: 55P0251 is a novel compound with blood glucose lowering activity in mice, which has been developed from a molecular backbone structure found in herbal remedies. We here report its basic pharmacological attributes and initial progress in unmasking the mode of action. MATERIALS AND METHODS: Pharmacokinetic properties of 55P0251 were portrayed in several species. First efforts to elucidate the glucose lowering mechanism in rodents included numerous experimental protocols dealing with glucose tolerance, insulin secretion from isolated pancreatic islets, and comparison to established drugs...
February 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28207725/ethnic-and-geographic-variations-in-the-incidence-of-pancreatitis-and-post-pancreatitis-diabetes-mellitus-in-new-zealand-a-nationwide-population-based-study
#7
Sayali A Pendharkar, Juby Mathew, Jinfeng Zhao, John A Windsor, Daniel J Exeter, Maxim S Petrov
AIM: To determine the incidence of acute pancreatitis (AP), chronic pancreatitis (CP), and post-pancreatitis diabetes mellitus (DP) in New Zealand, and the effect of ethnic and geographic variations. METHODS: Data were collected from all district health boards in New Zealand by the Ministry of Health (Manatū Hauora). Diagnosis of AP, CP and DP was determined by the International Classification of Diseases-10 codes. Incidence rates per 100,000 population per year were calculated using incident AP, CP and DP cases as the numerator, and the adult resident population of New Zealand as the denominator...
February 17, 2017: New Zealand Medical Journal
https://www.readbyqxmd.com/read/28207637/the-efficacy-of-a-prevascularized-retrievable-poly-d-l-lactide-co-%C3%AE%C2%B5-caprolactone-subcutaneous-scaffold-as-transplantation-site-for-pancreatic-islets
#8
Alexandra M Smink, Shiri Li, Don T Hertsig, Bart J de Haan, Leendert Schwab, Aart A van Apeldoorn, Eelco de Koning, Marijke M Faas, Jonathan R T Lakey, Paul de Vos
BACKGROUND: The liver as transplantation site for human pancreatic islets is a harsh microenvironment for islets and it lacks the ability to retrieve the graft. A retrievable, extrahepatic transplantation site that mimics the pancreatic environment is desired. Ideally this transplantation site should be located subdermal for easy surgical-access but this never resulted in normoglycemia. Here we describe the design and efficacy of a novel prevascularized, subcutaneously implanted, retrievable poly (D,L-lactide-co-ε-caprolactone) (PDLLCL) scaffold...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28205028/the-outcomes-of-initial-endoscopic-transluminal-drainage-are-superior-to-percutaneous-drainage-for-patients-with-infected-pancreatic-necrosis-a-prospective-cohort-study
#9
Wen-Hua He, Yong Zhu, Yin Zhu, Pi Liu, Hao Zeng, Liang Xia, Chen Yu, Hai-Ming Chen, Xu Shu, Zhi-Jian Liu, You-Xiang Chen, Nong-Hua Lu
BACKGROUND AND STUDY AIM: The commonly used minimally invasive methods for patients with infected pancreatic necrosis (IPN) are initial endoscopic transluminal drainage (ETD) and percutaneous catheter drainage (PCD), which are followed, if necessary, by endoscopic or surgical necrosectomy. This study intends to explore which of the two minimally invasive treatments leads to a better prognosis. PATIENTS AND METHODS: Patients with IPN and an indication for intervention were prospectively enrolled and underwent either initial ETD or PCD followed, if necessary, by endoscopic or surgical necrosectomy...
February 15, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28202581/identification-and-functional-implications-of-sodium-myo-inositol-cotransporter-1-in-pancreatic-beta-cells-and-type-2-diabetes-mellitus
#10
Stephen Yu Ting Li, Sam Tsz Wai Cheng, Dan Zhang, Po Sing Leung
Myo-inositol (MI), the precursor of the second messenger phosphoinositide (PI), mediates multiple cellular events. Rat islets exhibit active transport of MI, though the mechanism involved remains elusive. Here, we report, for the first time, the expression of sodium/myo-inositol cotransporter 1 (SMIT1) in rat islets and specifically, β-cells. Genetic or pharmacological inhibition of SMIT impaired glucose-stimulated insulin secretion by INS-1E cells, probably via down-regulation of PI signaling. Additionally, we found that SMIT1 expression in INS-1E cells and isolated islets was augmented by acute high-glucose exposure and reduced in chronic hyperglycemia conditions...
February 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28202288/tiam1-vav2-rac1-axis-a-tug-of-war-between-islet-function-and-dysfunction
#11
REVIEW
Anjaneyulu Kowluru
Glucose-stimulated insulin secretion [GSIS] from the islet β-cell involves a well-orchestrated interplay between metabolic and cationic events. It is well established that intracellular generation of adenine and guanine nucleotide triphosphates [e.g., ATP and GTP] represents one of the requisite signaling steps in GSIS. The small molecular mass GTP-binding proteins [G-proteins; e.g., Rac1 and Cdc42] have been shown to regulate islet β-cell function including actin cytoskeletal remodeling and fusion of insulin granules with the plasma membrane for GSIS to occur...
February 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28202025/mild-electrical-stimulation-with-heat-shock-guides-differentiation-of-embryonic-stem-cells-into-pdx1-expressing-cells-within-the-definitive-endoderm
#12
Tomoaki Koga, Nobuaki Shiraki, Shuichiro Yano, Mary Ann Suico, Saori Morino-Koga, Takashi Sato, Tsuyoshi Shuto, Shoen Kume, Hirofumi Kai
BACKGROUND: Because of the increasing number of diabetic patients, it is important to generate pancreatic and duodenal homeobox gene 1 (Pdx1)-expressing cells, which are capable of differentiating into pancreatic endocrine β cells. Mild electrical stimulation was reported to modulate the differentiation of ES cells into ectoderm-derived neuronal cells or mesoderm-derived cardiac cells. RESULTS: In this study, we report that mild electrical stimulation with heat shock (MET) potentiates the differentiation of ES cells into definitive endoderm-derived Pdx1-expressing cells...
February 15, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28198796/carbonic-anhydrase-i-and-ii-autoantibodies-in-beh%C3%A3-et-s-disease
#13
Ahmet Mentese, Ahmet Alver, Selim Demir, Aysegul Sumer, Serap Ozer Yaman, Murat Karkucak, Arzu Aydin Capkin, Diler Us Altay, Ibrahim Turan
BACKGROUND: Behçet's disease is a vasculitis, seen more frequently around the Mediterranean and the Far East, and evinces with oral and genital ulcerations, skin lesions and uveitis. Carbonic anhydrase (CA) is a metalloenzyme which is widely distributed in the living world, and it is essential for the regulation of acid-base balance. Anti-CA antibodies have been reported in many disorders, such as systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, endometriosis, idiopathic chronic pancreatitis, type 1 diabetes and Graves' disease...
December 3, 2016: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/28198575/tat-biliverdin-reductase-a-protects-ins-1-cells-from-human-islet-amyloid-polypeptide-induced-cytotoxicity-by-alleviating-oxidative-stress-and-er-stress
#14
Su Jin Lee, Hyung Kyung Kang, Won Sik Eum, Jinseu Park, Soo Young Choi, Hyeok Yil Kwon
Human islet amyloid polypeptide (hIAPP), a major constituent of islet amyloid deposits, induces pancreatic β-cell apoptosis and eventually contributes to β-cell deficit in patients with type 2 diabetes mellitus (T2DM). In this study, Tat-mediated transduction of biliverdin reductase A (BLVRA) was investigated in INS-1 cells to examine whether exogenous supplementation of BLVRA prevented hIAPP-induced apoptosis and dysfunction in insulin secretion in β-cells. Tat-BLVRA fusion protein was efficiently delivered into INS-1 cells in a time- and dose-dependent manner...
February 15, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28197316/design-and-synthesis-of-novel-selective-gpr40-agopams
#15
Christopher W Plummer, Matthew J Clements, Helen Chen, Murali Rajagopalan, Hubert Josien, William K Hagmann, Michael Miller, Maria E Trujillo, Melissa Kirkland, Daniel Kosinski, Joel Mane, Michele Pachanski, Boonlert Cheewatrakoolpong, Andrew F Nolting, Robert Orr, Melodie Christensen, Louis-Charles Campeau, Michael J Wright, Randal Bugianesi, Sarah Souza, Xiaoping Zhang, Jerry Di Salvo, Adam B Weinglass, Richard Tschirret-Guth, Ravi Nargund, Andrew D Howard, Steven L Colletti
GPR40 is a G-protein-coupled receptor expressed primarily in pancreatic islets and intestinal L-cells that has been a target of significant recent therapeutic interest for type II diabetes. Activation of GPR40 by partial agonists elicits insulin secretion only in the presence of elevated blood glucose levels, minimizing the risk of hypoglycemia. GPR40 agoPAMs have shown superior efficacy to partial agonists as assessed in a glucose tolerability test (GTT). Herein, we report the discovery and optimization of a series of potent, selective GPR40 agoPAMs...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28196600/genome-editing-in-hpscs-reveals-gata6-haploinsufficiency-and-a-genetic-interaction-with-gata4-in-human-pancreatic-development
#16
Zhong-Dong Shi, Kihyun Lee, Dapeng Yang, Sadaf Amin, Nipun Verma, Qing V Li, Zengrong Zhu, Chew-Li Soh, Ritu Kumar, Todd Evans, Shuibing Chen, Danwei Huangfu
Human disease phenotypes associated with haploinsufficient gene requirements are often not recapitulated well in animal models. Here, we have investigated the association between human GATA6 haploinsufficiency and a wide range of clinical phenotypes that include neonatal and adult-onset diabetes using CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9-mediated genome editing coupled with human pluripotent stem cell (hPSC) directed differentiation. We found that loss of one GATA6 allele specifically affects the differentiation of human pancreatic progenitors from the early PDX1+ stage to the more mature PDX1+NKX6...
February 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28196020/the-prevalence-and-clinicopathological-characteristics-of-high-grade-pancreatic-intraepithelial-neoplasia-autopsy-study-evaluating-the-entire-pancreatic-parenchyma
#17
Yoko Matsuda, Toru Furukawa, Shinichi Yachida, Makoto Nishimura, Atsuko Seki, Keisuke Nonaka, Junko Aida, Kaiyo Takubo, Toshiyuki Ishiwata, Wataru Kimura, Tomio Arai, Mari Mino-Kenudson
OBJECTIVE: We sought to identify clinicopathological characteristics of high-grade pancreatic intraepithelial neoplasia (PanIN)/carcinoma in situ to facilitate screening for pancreatic ductal adenocarcinoma. METHODS: We evaluated PanIN lesions in 173 consecutive autopsy cases with no evidence of pancreatic ductal adenocarcinoma and/or intraductal papillary mucinous neoplasm (mean age, 80.5 years) by submitting the entire pancreas for microscopic examination. RESULTS: PanIN-3 was found in 4% of examined cases, whereas PanIN-1 and PanIN-2 were present in 77% and 28%, respectively...
February 14, 2017: Pancreas
https://www.readbyqxmd.com/read/28193997/stepwise-reprogramming-of-liver-cells-to-a-pancreas-progenitor-state-by-the-transcriptional-regulator-tgif2
#18
Nuria Cerdá-Esteban, Heike Naumann, Silvia Ruzittu, Nancy Mah, Igor M Pongrac, Corinna Cozzitorto, Angela Hommel, Miguel A Andrade-Navarro, Ezio Bonifacio, Francesca M Spagnoli
The development of a successful lineage reprogramming strategy of liver to pancreas holds promises for the treatment and potential cure of diabetes. The liver is an ideal tissue source for generating pancreatic cells, because of its close developmental origin with the pancreas and its regenerative ability. Yet, the molecular bases of hepatic and pancreatic cellular plasticity are still poorly understood. Here, we report that the TALE homeoprotein TGIF2 acts as a developmental regulator of the pancreas versus liver fate decision and is sufficient to elicit liver-to-pancreas fate conversion both ex vivo and in vivo...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28193859/genetic-regulatory-signatures-underlying-islet-gene-expression-and-type-2-diabetes
#19
Arushi Varshney, Laura J Scott, Ryan P Welch, Michael R Erdos, Peter S Chines, Narisu Narisu, Ricardo D'O Albanus, Peter Orchard, Brooke N Wolford, Romy Kursawe, Swarooparani Vadlamudi, Maren E Cannon, John P Didion, John Hensley, Anthony Kirilusha, Lori L Bonnycastle, D Leland Taylor, Richard Watanabe, Karen L Mohlke, Michael Boehnke, Francis S Collins, Stephen C J Parker, Michael L Stitzel
Genome-wide association studies (GWAS) have identified >100 independent SNPs that modulate the risk of type 2 diabetes (T2D) and related traits. However, the pathogenic mechanisms of most of these SNPs remain elusive. Here, we examined genomic, epigenomic, and transcriptomic profiles in human pancreatic islets to understand the links between genetic variation, chromatin landscape, and gene expression in the context of T2D. We first integrated genome and transcriptome variation across 112 islet samples to produce dense cis-expression quantitative trait loci (cis-eQTL) maps...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193789/enriching-islet-phospholipids-with-eicosapentaenoic-acid-reduces-prostaglandin-e2-signaling-and-enhances-diabetic-%C3%AE-cell-function
#20
Joshua C Neuman, Michael D Schaid, Allison L Brill, Rachel J Fenske, Carly R Kibbe, Danielle A Fontaine, Sophia M Sdao, Harpreet K Brar, Kelsey M Connors, Haley N Wienkes, Kevin W Eliceiri, Matthew J Merrins, Dawn B Davis, Michelle E Kimple
Prostaglandin E2 (PGE2) is derived from arachidonic acid, while PGE3 is derived from eicosapentaenoic acid (EPA) using the same downstream metabolic enzymes. Little is known about the impact of EPA and PGE3 on β-cell function, particularly in the diabetic state. In this work, we determined PGE3 elicits a 10-fold weaker reduction in glucose-stimulated insulin secretion through the EP3 receptor as compared to PGE2 We tested the hypothesis that enriching pancreatic islet cell membranes with EPA, thereby reducing arachidonic acid abundance, would positively impact β-cell function in the diabetic state...
February 13, 2017: Diabetes
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