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https://www.readbyqxmd.com/read/27912756/mechanisms-of-inflammatory-responses-and-development-of-insulin-resistance-how-are-they-interlinked
#1
Kanwal Rehman, Muhammad Sajid Hamid Akash
BACKGROUND: Insulin resistance (IR) is one of the major hallmark for pathogenesis and etiology of type 2 diabetes mellitus (T2DM). IR is directly interlinked with various inflammatory responses which play crucial role in the development of IR. Inflammatory responses play a crucial role in the pathogenesis and development of IR which is one of the main causative factor for the etiology of T2DM. METHODS: A comprehensive online English literature was searched using various electronic search databases...
December 3, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27905899/a-case-of-extragastrointestinal-stromal-tumor-complicated-by-severe-hypoglycemia-a-unique-presentation-of-a-rare-tumor
#2
Zeb Saeed, Solaema Taleb, Carmella Evans-Molina
BACKGROUND: Non-Islet Cell Tumor Hypoglycemia (NICTH) is a rare paraneoplastic cause of hypoglycemia arising from excess tumor production of insulin-like growth factor. The objective of this report is to describe an unusual case of Extragastrointestinal Stromal Tumor (EGIST) associated NICTH. CASE PRESENTATION: A 64 year-old African female was brought to the emergency room with a 1-month history of recurrent syncope, weight loss, and abdominal bloating. Serum blood glucose was discovered to 39 mg/dL, when insulin, proinsulin, and C-peptide were suppressed...
December 1, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27893617/differential-role-of-b-cells-and-il-17-versus-ifn-%C3%AE-during-early-and-late-rejection-of-pig-islet-xenografts-in-mice
#3
Hee Kap Kang, Shusen Wang, Anil Dangi, Xiaomin Zhang, Amar Singh, Lei Zhang, James M Rosati, Wilma Suarez-Pinzon, Xuelian Deng, Xiaoyan Chen, Edward B Thorp, Bernhard J Hering, Stephen D Miller, Xunrong Luo
BACKGROUND: Xenogeneic islet transplantation is an emerging therapeutic option for diabetic patients. However, immunological tolerance to xenogeneic islets remains a challenge. METHODS: The current study used a pig-to-mouse discordant xenogeneic islet transplant model to examine anti-donor xenogeneic immune responses during early and late rejection, and to determine experimental therapeutic interventions that promote durable pig islet xenograft survival. RESULTS: We found that during early acute rejection of pig islet xenografts, the rejecting hosts exhibited a heavy graft infiltration with B220 B cells and a robust anti-pig antibody production...
November 23, 2016: Transplantation
https://www.readbyqxmd.com/read/27883367/a-drop-in-the-circulating-concentrations-of-soluble-receptor-for-ages-is-associated-with-seroconversion-to-autoantibody-positivity-but-not-with-subsequent-progression-to-clinical-disease-in-children-en-route-to-type-1-diabetes
#4
K M Salonen, S J Ryhänen, J M Forbes, T Härkönen, J Ilonen, O Simell, R Veijola, P-H Groop, M Knip
BACKGROUND: Advanced glycation end products (AGEs) and their interaction with the receptor for advanced glycation end products (RAGE) have been studied for their role in the pathogenesis and complications of type 1 diabetes. Decreased concentrations of soluble RAGE (sRAGE) have been reported in acute autoimmune inflammation. We set out to analyze the changes in (sRAGE) concentration during preclinical diabetes in children seroconverting to islet autoantibody positivity. METHODS: We measured serum concentrations of sRAGE in 168 children who progressed to clinical disease and 43 children who turned positive for at least two diabetes-associated autoantibodies but remained non-diabetic...
November 24, 2016: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/27883079/a-parasite-derived-68-mer-peptide-ameliorates-autoimmune-disease-in-murine-models-of-type-1-diabetes-and-multiple-sclerosis
#5
Maria E Lund, Judith Greer, Aakanksha Dixit, Raquel Alvarado, Padraig McCauley-Winter, Joyce To, Akane Tanaka, Andrew T Hutchinson, Mark W Robinson, Ann M Simpson, Bronwyn A O'Brien, John P Dalton, Sheila Donnelly
Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27875339/apolipoprotein-ciii-is-a-new-player-in-diabetes
#6
Lisa Juntti-Berggren, Per-Olof Berggren
PURPOSE OF REVIEW: Type-1 and type-2 diabetes are diseases with an increasing number of patients and a complex, multifactorial pathogenesis. Apolipoprotein (apo) CIII is increased in both types of diabetes and interventions preventing the increase have effects on the development of diabetes. RECENT FINDINGS: ApoCIII affects intracellular Ca-handling by activating voltage-gated Ca-channels. ApoCIII is produced within the pancreatic islets and it increases in parallel with the development of insulin resistance and type-2 diabetes...
November 21, 2016: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27872297/singular-role-for-t-bet-cxcr3-regulatory-t-cells-in-protection-from-autoimmune-diabetes
#7
Tze Guan Tan, Diane Mathis, Christophe Benoist
Foxp3(+) regulatory T (Treg) cells are crucial for restraining inflammation in a variety of autoimmune diseases, including type 1 diabetes (T1D). However, the transcriptional and functional phenotypes of Treg cells within the pancreatic lesion remain poorly understood. Here we characterized pancreas-infiltrating Treg cells in the NOD mouse model of T1D and uncovered a substantial enrichment of the Treg subpopulation expressing the chemokine receptor CXCR3. Accumulation of CXCR3(+) Treg cells within pancreatic islets was dependent on the transcription factor T-BET, and genetic ablation of T-BET increased the onset and penetrance of disease, abrogating the sex bias normally seen in the NOD model...
November 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27851770/direct-stimulation-of-islet-insulin-secretion-by-glycolytic-and-mitochondrial-metabolites-in-kcl-depolarized-islets
#8
Javier Pizarro-Delgado, Jude T Deeney, Barbara E Corkey, Jorge Tamarit-Rodriguez
We have previously demonstrated that islet depolarization with 70 mM KCl opens Cx36 hemichannels and allows diffusion of small metabolites and cofactors through the β-cell plasma membrane. We have investigated in this islet "permeabilized" model whether glycolytic and citric acid cycle intermediates stimulate insulin secretion and how it correlates with ATP production (islet content plus extracellular nucleotide accumulation). Glycolytic intermediates (10 mM) stimulated insulin secretion and ATP production similarly...
2016: PloS One
https://www.readbyqxmd.com/read/27846886/antidiabetic-and-hypolipidemic-activities-of-hydroethanolic-root-extract-of-uvaria-chamae-in-streptozotocin-induced-diabetic-albino-rats
#9
Jonathan Emeka Emordi, Esther Oluwatoyin Agbaje, Ibrahim Adekunle Oreagba, Osede Ignis Iribhogbe
BACKGROUND: Diabetes mellitus is a metabolic disorder of multiple aetiology characterised by hyperglycemia resulting from defects in insulin secretion, insulin action or both. It is a global epidemic ravaging both developed and developing countries. The situation will worsen if nothing is done urgently. In fact, the need to identify natural products with antidiabetic potentials is of great importance as supported by several research efforts all over the world, in search of antidiabetic plant based products that are safe and efficacious...
November 15, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27829285/immunomodulation-of-cell-penetrating-tat-metallothionein-for-successful-outcome-of-xenotransplanted-pancreatic-islet
#10
Min Jun Kim, Yong Hwa Hwang, Yong Hee Kim, Dong Yun Lee
Pancreatic islet transplantation is a promising treatment for treatment of type 1 diabetes; however, transplantation outcomes have been disappointing due to early graft loss that is mediated by many immune responses. Immune cells not only directly damaged islet but also produced reactive oxygen species (ROS), which is highly toxic to islet cells. Metallothionein (MT) can provide protection against oxidative stress by scavenging various range of ROS including superoxide, hydroxyl radical, hydrogen peroxide, and nitric oxide...
November 10, 2016: Journal of Drug Targeting
https://www.readbyqxmd.com/read/27820841/metformin-ameliorates-dysfunctional-traits-of-glibenclamide-and-glucose-induced-insulin-secretion-by-suppression-of-imposed-overactivity-of-the-islet-nitric-oxide-synthase-no-system
#11
Ingmar Lundquist, Israa Mohammed Al-Amily, Sandra Meidute Abaraviciene, Albert Salehi
Metformin lowers diabetic blood glucose primarily by reducing hepatic gluconeogenesis and increasing peripheral glucose uptake. However, possible effects by metformin on beta-cell function are incompletely understood. We speculated that metformin might positively influence insulin secretion through impacting the beta-cell nitric oxide synthase (NOS)-NO system, a negative modulator of glucose-stimulated insulin release. In short-time incubations with isolated murine islets either glibenclamide or high glucose augmented insulin release associated with increased NO production from both neural and inducible NOS...
2016: PloS One
https://www.readbyqxmd.com/read/27818936/suppressing-hyperinsulinemia-prevents-obesity-but-causes-rapid-onset-of-diabetes-in-leptin-deficient-lep-ob-ob-mice
#12
Anna M D'souza, James D Johnson, Susanne M Clee, Timothy J Kieffer
OBJECTIVE: Hyperinsulinemia is commonly associated with obesity. Mice deficient in the adipose-derived hormone leptin (Lep(ob/ob)) develop hyperinsulinemia prior to onset of obesity and glucose intolerance. Whether the excess of circulating insulin is a major contributor to obesity and impaired glucose homeostasis in Lep(ob/ob) mice is unclear. It has been reported previously that diet-induced obesity in mice can be prevented by reducing insulin gene dosage. In the present study, we examined the effects of genetic insulin reduction in Lep(ob/ob) mice on circulating insulin, body composition, and glucose homeostasis...
November 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27810340/anti-diabetic-activity-of-holothuria-thomasi-saponin
#13
Amira R El Barky, Samy A Hussein, Abeer A Alm-Eldeen, Yehia A Hafez, Tarek M Mohamed
BACKGROUND: Diabetes mellitus represents a global health problem. It characterized by hyperglycemia that induces oxidative stress leading to a generation of free radicals. A wide variety of natural products in plants and other marine animals represent antioxidant activity and other health benefits like those of sea cucumber. Therefore, this study aimed to investigate the antidiabetic activity of glycosidic compound - saponin - derived from the Egyptian sea cucumber, Holothuria thomasi...
October 31, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27810111/embryonic-exposures-to-perfluorooctanesulfonic-acid-pfos-disrupt-pancreatic-organogenesis-in-the-zebrafish-danio-rerio
#14
Karilyn E Sant, Haydee M Jacobs, Katrina A Borofski, Jennifer B Moss, Alicia R Timme-Laragy
Perfluorooctanesulfonic acid (PFOS) is a ubiquitous environmental contaminant, previously utilized as a non-stick application for consumer products and firefighting foam. It can cross the placenta, and has been repeatedly associated with increased risk for diabetes in epidemiological studies. Here, we sought to establish the hazard posed by embryonic PFOS exposures on the developing pancreas in a model vertebrate embryo, and develop criteria for an adverse outcome pathway (AOP) framework to study the developmental origins of metabolic dysfunction...
October 31, 2016: Environmental Pollution
https://www.readbyqxmd.com/read/27803236/melatonin-modifies-basal-and-stimulated-insulin-secretion-via-nadph-oxidase
#15
Daniel Simões, Patrícia Riva, Rodrigo Antonio Peliciari-Garcia, Vinicius Fernandes Cruzat, Maria Fernanda Graciano, Ana Claudia Munhoz, Marco Taneda, José Cipolla-Neto, Angelo Rafael Carpinelli
Melatonin is a hormone synthesized in the pineal gland, which modulates several functions within the organism, including the synchronization of glucose metabolism and glucose-stimulated insulin secretion (GSIS). Melatonin can mediate different signaling pathways in pancreatic islets through two membrane receptors and via antioxidant or pro-oxidant enzymes modulation. NADPH oxidase (NOX) is a pro-oxidant enzyme responsible for the production of the reactive oxygen specie (ROS) superoxide, generated from molecular oxygen...
December 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27801610/kmt2a-cooperates-with-menin-to-suppress-tumorigenesis-in-mouse-pancreatic-islets
#16
Wenchu Lin, Joshua M Francis, Hong Li, Xiaoping Gao, Chandra Sekhar Pedamallu, Patricia Ernst, Matthew Meyerson
The reported incidence of pancreatic neuroendocrine tumors (PanNETs) has increased, due in large part to improvements in detection and awareness. However, therapeutic options are limited and a critical need exists for understanding a more thorough characterization of the molecular pathology underlying this disease. The Men1 knockout mouse model recapitulates the early stage of human PanNET development and can serve as a foundation for the development of advanced mouse models that are necessary for preclinical testing...
November 1, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27797910/islet-expressed-cxcl10-promotes-autoimmune-destruction-of-islet-iso-grafts-in-mice-with-type-1-diabetes
#17
Christine Bender, Selina Christen, Klaus Scholich, Monika Bayer, Josef M Pfeilschifter, Edith Hintermann, Urs Christen
Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β-cells in the pancreas. Thereby the chemokine CXC-motif ligand 10 (CXCL10) plays an important role in the recruitment of autoaggressive lymphocytes to the islets of Langerhans. Transplantation of isolated islets as a promising therapy of T1D has been hampered by early graft rejection. Here, we investigated the influence of CXCL10 on the autoimmune destruction of islet iso-grafts using RIP-LCMV mice expressing a lymphocytic choriomeningitis virus (LCMV) protein in the β-cells...
October 26, 2016: Diabetes
https://www.readbyqxmd.com/read/27796637/how-to-make-insulin-producing-pancreatic-%C3%AE-cells-for-diabetes-treatment
#18
REVIEW
Jiaqi Lu, Qing Xia, Qiao Zhou
Around 400 million people worldwide suffer from diabetes mellitus. The major pathological event for Type 1 diabetes and advanced Type 2 diabetes is loss or impairment of insulin-secreting β cells of the pancreas. For the past 100 years, daily insulin injection has served as a life-saving treatment for these patients. However, insulin injection often cannot achieve full glucose control, and over time poor glucose control leads to severe complications and mortality. As an alternative treatment, islet transplantation has been demonstrated to effectively maintain glucose homeostasis in diabetic patients, but its wide application is limited by the scarcity of donated islets...
October 27, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27790217/cholinergic-stimulation-prevents-the-development-of-autoimmune-diabetes-evidence-for-the-modulation-of-th17-effector-cells-via-an-ifn%C3%AE-dependent-mechanism
#19
Junu A George, Ghada Bashir, Mohammed M Qureshi, Yassir A Mohamed, Jamil Azzi, Basel K Al-Ramadi, Maria J Fernández-Cabezudo
Type I diabetes (T1D) results from T cell-mediated damage of pancreatic β-cells and loss of insulin production. The cholinergic anti-inflammatory pathway represents a physiological link connecting the central nervous and immune systems via vagus nerve, and functions to control the release of proinflammatory cytokines. Using the multiple low-dose streptozotocin (MLD-STZ) model to induce experimental autoimmune diabetes, we investigated the potential of regulating the development of hyperglycemia through administration of paraoxon, a highly specific acetylcholinesterase inhibitor (AChEI)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27777971/anti-coreceptor-therapy-drives-selective-t-cell-egress-by-suppressing-inflammation-dependent-chemotactic-cues
#20
Aaron J Martin, Matthew Clark, Gregory Gojanovich, Fatima Manzoor, Keith Miller, Douglas E Kline, Y Maurice Morillon, Bo Wang, Roland Tisch
There continues to be a need for immunotherapies to treat type 1 diabetes in the clinic. We previously reported that nondepleting anti-CD4 and -CD8 Ab treatment effectively reverses diabetes in new-onset NOD mice. A key feature of the induction of remission is the egress of the majority of islet-resident T cells. How this occurs is undefined. Herein, the effects of coreceptor therapy on islet T cell retention were investigated. Bivalent Ab binding to CD4 and CD8 blocked TCR signaling and T cell cytokine production, while indirectly downregulating islet chemokine expression...
October 20, 2016: JCI Insight
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