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https://www.readbyqxmd.com/read/29158477/sirolimus-induces-depletion-of-intracellular-calcium-stores-and-mitochondrial-dysfunction-in-pancreatic-beta-cells
#1
Angela Lombardi, Jessica Gambardella, Xue-Liang Du, Daniela Sorriento, Maurizio Mauro, Guido Iaccarino, Bruno Trimarco, Gaetano Santulli
Sirolimus (rapamycin) is an immunosuppressive drug used in transplantation. One of its major side effects is the increased risk of diabetes mellitus; however, the exact mechanisms underlying such association have not been elucidated. Here we show that sirolimus impairs glucose-stimulated insulin secretion both in human and murine pancreatic islets and in clonal β cells in a dose- and time-dependent manner. Importantly, we demonstrate that sirolimus markedly depletes calcium (Ca(2+)) content in the endoplasmic reticulum and significantly decreases glucose-stimulated mitochondrial Ca(2+) uptake...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29157116/perinatal-exposure-to-high-dietary-advanced-glycation-end-products-in-transgenic-nod8-3-mice-leads-to-pancreatic-beta-cell-dysfunction
#2
Danielle J Borg, Felicia Y T Yap, Sahar Keshvari, David G Simmons, Linda A Gallo, Amelia K Fotheringham, Aowen Zhuang, Robyn M Slattery, Sumaira Z Hasnain, Melinda T Coughlan, Phillip Kantharidis, Josephine M Forbes
The contribution of environmental factors to pancreatic islet damage in type 1 diabetes remains poorly understood. In this study, we crossed mice susceptible to type 1 diabetes, where parental male (CD8(+) T cells specific for IGRP206-214; NOD8.3) and female (NOD/ShiLt) mice were randomized to a diet either low or high in AGE content and maintained on this diet throughout pregnancy and lactation. After weaning, NOD8.3(+) female offspring were identified and maintained on the same parental feeding regimen for until day 28 of life...
November 20, 2017: Islets
https://www.readbyqxmd.com/read/29150935/generation-of-insulin-producing-cells-from-human-adipose-derived-mesenchymal-stem-cells-on-pva-scaffold-by-optimized-differentiation-protocol
#3
Seyed Ehsan Enderami, Masoud Soleimani, Yousef Mortazavi, Samad Nadri, Ali Salimi
The studies have been done on patient-specific human adipose-derived from mesenchymal stem cells (hADSCs) like a series of autologous growth factors and nanofibrous scaffolds (3D culture) will probably have many benefits for regenerative medicine in type 1 diabetes mellitus (TIDM) patients in the future. For this purpose, we established a polyvinyl alcohol (PVA) scaffold and a differentiation protocol by adding platelet-rich plasma (PRP) that induces the hADSCs into insulin-producing cells (IPCs). The Characteristics of the derived IPCs in 3D culture were compared with conventional culture (2D) groups evaluated at the mRNA and protein levels...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150402/network-science-of-biological-systems-at-different-scales-a-review
#4
REVIEW
Marko Gosak, Rene Markovič, Jurij Dolenšek, Marjan Slak Rupnik, Marko Marhl, Andraž Stožer, Matjaž Perc
Network science is today established as a backbone for description of structure and function of various physical, chemical, biological, technological, and social systems. Here we review recent advances in the study of complex biological systems that were inspired and enabled by methods of network science. First, we present research highlights ranging from determination of the molecular interaction network within a cell to studies of architectural and functional properties of brain networks and biological transportation networks...
November 3, 2017: Physics of Life Reviews
https://www.readbyqxmd.com/read/29149826/novel-functions-of-microrna-17-92-cluster-in-the-endocrine-system
#5
Shan Wan, Xiang Chen, Yuedong He, Xijie Yu
BACKGROUND: MiR-17-92 cluster is coded by MIR17HG in chromosome 13, which is highly conserved in vertebrates. Published literatures have proved that miR-17-92 cluster critically regulates tumorigenesis and metastasis. Recent researches showed that the miR-17-92 cluster also plays novel functions in the endocrine system. OBJECTIVE: To summarize recent findings on the physiological and pathological roles of miR-17-92 cluster in bone, lipid and glucose metabolisms...
November 17, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/29140125/diabetes-area-patent-participation-analysis-part-ii-years-2011-2016
#6
Markus Boehm, Matthew Crawford, Jamie E Moscovitz, Philip A Carpino
Diabetes is a metabolic disease characterized by elevated levels of plasma glucose. When untreated, diabetes increases the risk of developing co-morbidities such as cardiovascular disease. Several drugs, often used as part of combination therapies, have been approved to treat the disease, but these drugs will eventually fail to effectively control blood glucose levels, at which point insulin replacement therapy is required. A medical need exists for new anti-diabetic drugs that exhibit good efficacy with improved safety/toleration profiles and can be added on top of existing therapies, or that can provide additional benefits beyond glucose lowering such as pancreatic beta (β)-cell protection...
November 15, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29136166/diabetes-induced-hyperglycemia-impairs-male-reproductive-function-a-systematic-review
#7
Constanze C Maresch, Dina C Stute, Marco G Alves, Pedro F Oliveira, David M de Kretser, Thomas Linn
BACKGROUND: Hyperglycemia can result from a loss of pancreatic beta-cells or a decline in their function leading to decreased insulin secretion or may arise from insulin resistance and variable degrees of inadequate insulin secretion resulting in diabetes and related comorbidities. To date several reviews have addressed the issue of diabetes-related male infertility but most have focused on how metabolic syndrome causes the decline in male fertility. However, a comprehensive overview as to how diabetes-induced hyperglycemia impairs male fertility is missing...
November 10, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/29134977/metformin-effects-are-augmented-by-chronic-intermittent-cold-stress-in-high-fat-diet-fed-male-wistar-rats
#8
A O Ige, O I Iwaloye, E O Adewoye
This study investigated the effects of metformin on some glucose regulatory indices in high fat diet (HFD) fedmale Wistar rats exposed to room temperature and chronic intermittent cold stress (CICS). Thirty rats were randomly dividedinto 5 groups. Group 1(control) was maintained on standard rat chow while groups 2-5 were maintained on HFD for 8weeksrespectively prior to experimental procedures. Control, group 2(HFD untreated) and group 3(HFD+metformin (250mg/kg)were exposed to room temperature while groups 4(HFD untreated+CICS) and 5(HFD+CICS+metformin) were exposed toCICS for 21days...
June 30, 2017: Nigerian Journal of Physiological Sciences: Official Publication of the Physiological Society of Nigeria
https://www.readbyqxmd.com/read/29134606/intravenous-ferric-carboxymaltose-in-patients-with-type-2-diabetes-mellitus-and-iron-deficiency-clever-trial-study-design-and-protocol
#9
Christoph Schindler, Andreas L Birkenfeld, Markolf Hanefeld, Ulrike Schatz, Carsta Köhler, Martin Grüneberg, Diethelm Tschöpe, Matthias Blüher, Christoph Hasslacher, Stefan R Bornstein
INTRODUCTION: HbA1c is the gold standard for glycemic control in pre-diabetes and diabetes. However, its validity has been questioned, especially in the presence of imbalanced iron homeostasis. The CLEVER trial aims to evaluate the relationship between iron deficiency and HbA1c (a biomarker for the diagnosis and therapeutic monitoring of type 2 diabetes) in a randomized, placebo-controlled, multicenter clinical trial. METHODS: The CLEVER (intravenous ferric CarboxymaLtosE for improVement of mEtabolic parameters in type 2 diabetes patients with iRon deficiency) trial is a randomized, single-blind, proof-of-concept study with two treatment arms...
November 13, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29131920/congenital-hyperinsulinism
#10
Elena Minakova, Alison Chu
Congenital hyperinsulinism is a rare disorder that commonly presents in the immediate postnatal period as persistent hypoglycemia. The condition is frequently resistant to medical therapies, and the genetic mutations implicated in the disorder can be predictive of response to therapy. Evaluation of hypoglycemia in the illustrative case presented in this article led to genetic testing identifying recessive mutations in the potassium channel subunits of the beta-islet pancreatic cells. Potassium channel defects are often refractory to medical therapies, so near-total pancreatectomy is usually indicated; however, genetic mutations leading to metabolic dysregulation within the beta-islet pancreatic cells are usually responsive to medical therapy...
November 1, 2017: Pediatric Annals
https://www.readbyqxmd.com/read/29130725/-eighth-jes%C3%A3%C2%BAs-culebras-lecture-critical-care-nutrition-and-hyperglycemia-a-close-relationship
#11
Alfonso Mesejo
Critically ill patients show a metabolic response to injury that affects carbohydrate metabolism, causing hyperglycemia and an increase in glycemic variability that makes the critically ill patient susceptible to infection, resulting in morbidity and mortality increase. Also, severe hypoglycemia was detected as a consequence of intensive insulin treatment that provokes deleterious effects in their clinical evolution, so a correct monitoring of plasma glucose would contribute to reduce morbidity and mortality...
October 24, 2017: Nutrición Hospitalaria: Organo Oficial de la Sociedad Española de Nutrición Parenteral y Enteral
https://www.readbyqxmd.com/read/29129820/deactivation-of-the-nlrp3-inflammasome-in-infiltrating-macrophages-by-duodenal-jejunal-bypass-surgery-mediates-improvement-of-beta-cell-function-in-type-2-diabetes
#12
Dong Wu, Zhi-Bo Yan, Yu-Gang Cheng, Ming-Wei Zhong, Shao-Zhuang Liu, Guang-Yong Zhang, San-Yuan Hu
OBJECTIVE: Bariatric surgery could improve pancreatic beta cell function, thereby leading to the remission of the type 2 diabetes mellitus (T2DM). However, the specific mechanism underlying this phenomenon is yet to be revealed. The aim of this study is to test the hypothesis that Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in infiltrating macrophages plays an important role in the modulation of beta cell function after duodenal-jejunal bypass (DJB) surgery...
November 9, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29127288/novel-genetically-encoded-fluorescent-probes-enable-real-time-detection-of-potassium-in-vitro-and-in-vivo
#13
Helmut Bischof, Markus Rehberg, Sarah Stryeck, Katharina Artinger, Emrah Eroglu, Markus Waldeck-Weiermair, Benjamin Gottschalk, Rene Rost, Andras T Deak, Tobias Niedrist, Nemanja Vujic, Hanna Lindermuth, Ruth Prassl, Brigitte Pelzmann, Klaus Groschner, Dagmar Kratky, Kathrin Eller, Alexander R Rosenkranz, Tobias Madl, Nikolaus Plesnila, Wolfgang F Graier, Roland Malli
Changes in intra- and extracellular potassium ion (K(+)) concentrations control many important cellular processes and related biological functions. However, our current understanding of the spatiotemporal patterns of physiological and pathological K(+) changes is severely limited by the lack of practicable detection methods. We developed K(+)-sensitive genetically encoded, Förster resonance energy transfer-(FRET) based probes, called GEPIIs, which enable quantitative real-time imaging of K(+) dynamics. GEPIIs as purified biosensors are suitable to directly and precisely quantify K(+) levels in different body fluids and cell growth media...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29123178/a-nanobody-based-tracer-targeting-dpp6-for-non-invasive-imaging-of-human-pancreatic-endocrine-cells
#14
Alexander Balhuizen, Sam Massa, Iris Mathijs, Jean-Valery Turatsinze, Jens De Vos, Stéphane Demine, Catarina Xavier, Olatz Villate, Isabelle Millard, Dominique Egrise, Carmen Capito, Raphaël Scharfmann, Pieter In't Veld, Piero Marchetti, Serge Muyldermans, Serge Goldman, Tony Lahoutte, Luc Bouwens, Decio L Eizirik, Nick Devoogdt
There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29121068/metabolic-regulation-of-glp-1-and-pc1-3-in-pancreatic-%C3%AE-cell-line
#15
Veronica Sancho, Giuseppe Daniele, Daniela Lucchesi, Roberto Lupi, Annamaria Ciccarone, Giuseppe Penno, Cristina Bianchi, Angela Dardano, Roberto Miccoli, Stefano Del Prato
BACKGROUND AND AIMS: An intra-islet incretin system has been recently suggested to operate through modulation of the expression and activity of proconvertase 1/3 and 2 (PC1/3, PC2) in pancreatic alpha-cell accounting for local release of GLP-1. Little is known, whether this alpha-cell activity can be affected by the metabolic alterations occurring in type 2 diabetes, such as hyperglycemia, hyperlipidemia or hyperglucagonemia. MATERIALS AND METHODS: AlphaTC1/6 cells from a mice pancreatic cell line were incubated in the presence of two glucose (G) concentration (5...
2017: PloS One
https://www.readbyqxmd.com/read/29119245/development-and-characterisation-of-a-novel-glucagon-like-peptide-1-receptor-antibody
#16
Emma K Biggs, Lihuan Liang, Jacqueline Naylor, Shimona Madalli, Rachel Collier, Matthew P Coghlan, David J Baker, David C Hornigold, Peter Ravn, Frank Reimann, Fiona M Gribble
AIMS/HYPOTHESIS: Glucagon like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion by binding to GLP-1 receptors (GLP1Rs) on pancreatic beta cells. GLP-1 mimetics are used in the clinic for the treatment of type 2 diabetes, but despite their therapeutic success, several clinical effects of GLP-1 remain unexplained at a mechanistic level, particularly in extrapancreatic tissues. The aim of this study was to generate and characterise a monoclonal antagonistic antibody for the GLP1R for use in vivo...
November 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/29115211/measurement-of-gastrointestinal-hormones
#17
Nicolai J Wewer Albrechtsen
Towards the end of the 20th century, the number of subjects with diabetes and obesity rose exponentially. The discoveries of insulin- and appetite-modulating chemical signals, including glucagon-like peptide-1 (GLP-1), secreted from the gastrointestinal system, led to development of a new group of drugs which now are being used for glucose-lowering therapy and weight loss. Understanding of the physiology of gut derived signals and their pathophysiologi-cal importance requires accurate measurements of their circulat-ing levels...
November 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/29108266/the-systemic-tumor-response-to-rnase-a-treatment-affects-the-expression-of-genes-involved-in-maintaining-cell-malignancy
#18
Nadezhda Mironova, Olga Patutina, Evgenyi Brenner, Alexander Kurilshikov, Valentin Vlassov, Marina Zenkova
Recently, pancreatic RNase A was shown to inhibit tumor and metastasis growth that accompanied by global alteration of miRNA profiles in the blood and tumor tissue (Mironova et al., 2013). Here, we performed a whole transcriptome analysis of murine Lewis lung carcinoma (LLC) after treatment of tumor-bearing mice with RNase A. We identified 966 differentially expressed transcripts in LLC tumors, of which 322 were upregulated and 644 were downregulated after RNase A treatment. Many of these genes are involved in signaling pathways that regulate energy metabolism, cell-growth promoting and transforming activity, modulation of the cancer microenvironment and extracellular matrix components, and cellular proliferation and differentiation...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107594/genes-associated-with-pancreas-development-and-function-maintain-open-chromatin-in-ipscs-generated-from-human-pancreatic-beta-cells
#19
Matthias Thurner, Liraz Shenhav, Agata Wesolowska-Andersen, Amanda J Bennett, Amy Barrett, Anna L Gloyn, Mark I McCarthy, Nicola L Beer, Shimon Efrat
Current in vitro islet differentiation protocols suffer from heterogeneity and low efficiency. Induced pluripotent stem cells (iPSCs) derived from pancreatic beta cells (BiPSCs) preferentially differentiate toward endocrine pancreas-like cells versus those from fibroblasts (FiPSCs). We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq and identified ∼8.3k significant, differential open chromatin sites (DOCS) between the two iPSC subtypes (false discovery rate [FDR] < 0.05). DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS) were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR < 0...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29102899/hdl-functionality-in-type-1-diabetes
#20
REVIEW
Shiva Ganjali, Geesje M Dallinga-Thie, Luis E Simental-Mendía, Maciej Banach, Matteo Pirro, Amirhossein Sahebkar
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by absence of insulin secretion due to destruction of the pancreatic beta-cells. Patients with T1D exhibit an increased risk for cardiovascular disease (CVD) compared with non-diabetic subjects. It has been established that low concentration of high-density lipoprotein cholesterol (HDL-C), an independent risk marker of CVD, coincides with a reduced protective capacity against oxidative stress. However, conflicting results have been reported on the prevalence of low HDL-C levels in T1D...
October 21, 2017: Atherosclerosis
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