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Diabetes New Target

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https://www.readbyqxmd.com/read/27917261/anti-hepatitis-c-virus-drugs-and-kidney
#1
REVIEW
Paul Carrier, Marie Essig, Marilyne Debette-Gratien, Denis Sautereau, Annick Rousseau, Pierre Marquet, Jérémie Jacques, Véronique Loustaud-Ratti
Hepatitis C virus (HCV) mainly targets the liver but can also induce extrahepatic manifestations. The kidney may be impacted via an immune mediated mechanism or a cytopathic effect. HCV patients are clearly at a greater risk of chronic kidney disease (CKD) than uninfected patients are, and the presence of CKD increases mortality. Interferon-based therapies and ribavirin are difficult to manage and are poorly effective in end-stage renal disease and hemodialysis. These patients should be given priority treatment with new direct anti-viral agents (DAAs) while avoiding peginterferon and ribavirin...
November 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27916275/artemisinins-target-gabaa-receptor-signaling-and-impair-%C3%AE-cell-identity
#2
Jin Li, Tamara Casteels, Thomas Frogne, Camilla Ingvorsen, Christian Honoré, Monica Courtney, Kilian V M Huber, Nicole Schmitner, Robin A Kimmel, Roman A Romanov, Caterina Sturtzel, Charles-Hugues Lardeau, Johanna Klughammer, Matthias Farlik, Sara Sdelci, Andhira Vieira, Fabio Avolio, François Briand, Igor Baburin, Peter Májek, Florian M Pauler, Thomas Penz, Alexey Stukalov, Manuela Gridling, Katja Parapatics, Charlotte Barbieux, Ekaterine Berishvili, Andreas Spittler, Jacques Colinge, Keiryn L Bennett, Steffen Hering, Thierry Sulpice, Christoph Bock, Martin Distel, Tibor Harkany, Dirk Meyer, Giulio Superti-Furga, Patrick Collombat, Jacob Hecksher-Sørensen, Stefan Kubicek
Type 1 diabetes is characterized by the destruction of pancreatic β cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types, including glucagon-producing α cells. In a genetic model, loss of the master regulatory transcription factor Arx is sufficient to induce the conversion of α cells to functional β-like cells. Here, we identify artemisinins as small molecules that functionally repress Arx by causing its translocation to the cytoplasm...
November 30, 2016: Cell
https://www.readbyqxmd.com/read/27915042/non-coding-rnas-and-berberine-a-new-mechanism-of-its-anti-diabetic-activities
#3
REVIEW
Wenguang Chang
Type 2 Diabetes (T2D) is a metabolic disease with high mortality and morbidity. Non-coding RNAs, including small and long non-coding RNAs, are a novel class of functional RNA molecules that regulate multiple biological functions through diverse mechanisms. Studies in the last decade have demonstrated that non-coding RNAs may represent compelling therapeutic targets and play important roles in regulating the course of insulin resistance and T2D. Berberine, a plant-based alkaloid, has shown promise as an anti-hyperglycaemic, anti-hyperlipidaemic agent against T2D...
November 30, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27914923/alloantigen-gene-transfer-to-hepatocytes-promotes-tolerance-to-pancreatic-islet-graft-by-inducing-cd8-regulatory-t-cells
#4
Valentin Le Guen, Jean-Paul Judor, Françoise Boeffard, Vanessa Gauttier, Nicolas Ferry, Jean-Paul Soulillou, Sophie Brouard, Sophie Conchon
BACKGROUND & AIM: Induction of donor-specific immune tolerance is a good alternative to chronic life-long immunosuppression for transplant patients. Donor major histocompatibility complex (MHC) molecules represent the main targets of the allogeneic immune response of transplant recipients. Liver-targeted gene transfer with viral vectors induces tolerance toward the encoded antigen. The aim of this work was to determine whether alloantigen gene transfer to hepatocytes induces tolerance and promotes graft acceptance...
November 30, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27909794/prescription-of-oral-antidiabetic-drugs-in-tyrol-data-from-the-tyrol-diabetes-registry-2012-2015
#5
Lukas Lunger, Andreas Melmer, Willi Oberaigner, Marco Leo, Martin Juchum, Karin Pölzl, Johannes Gänzer, Martha Innerebner, Egon Eisendle, Gertrud Beck, Hermann Kathrein, Bernhard Heindl, Hans Robert Schönherr, Monika Lechleitner, Herbert Tilg, Christoph Ebenbichler
Diabetes mellitus affects 9% of the adult population worldwide and the economic burden of the disease is growing exponentially. In type 2 diabetes mellitus (T2DM), when life style interventions fail to achieve treatment targets, oral antidiabetic drugs are prescribed to improve glycemic control. Several new oral antidiabetics have been launched in the last few years, which enlarged the spectrum of available treatment options in T2DM. The present study aimed to examine T2DM treatment patterns in a cohort of 7769 patients recruited from the Diabetes Registry Tyrol (DRT) with at least one visit from 2012-2015...
December 1, 2016: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/27904682/targeting-cancer-cell-metabolism-the-combination-of-metformin-and-2-deoxyglucose-regulates-apoptosis-in-ovarian-cancer-cells-via-p38-mapk-jnk-signaling-pathway
#6
Jie Zhu, Ya Zheng, Haiyan Zhang, Hong Sun
Targeting cancer cell metabolism is a new promising strategy to fight cancer. Metformin, a first-line treatment for type 2 diabetes mellitus, exerts anti-cancer and anti-proliferative action. 2-deoxyglucose (2-DG), a glucose analog, works as a competitive inhibitor of glycolysis. In this study, we show for the first time that metformin in combination with 2-DG inhibited growth, migration, invasion and induced cell cycle arrest of ovarian cancer cells in vitro. Moreover, metformin and 2-DG could efficiently induce apoptosis in ovarian cancer cells, which was achieved by activating p38 MAPK and JNK pathways...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27900263/islet-chrebp-%C3%AE-is-increased-in-diabetes-and-controls-chrebp-%C3%AE-and-glucose-induced-gene-expression-via-a-negative-feedback-loop
#7
Gu Jing, Junqin Chen, Guanlan Xu, Anath Shalev
OBJECTIVE: Carbohydrate-response element-binding protein (ChREBP) is the major transcription factor conferring glucose-induced gene expression in pancreatic islets, liver and adipose tissue. Recently, a novel ChREBP isoform, ChREBP-β, was identified in adipose tissue and found to be also expressed in islets and involved in glucose-induced beta cell proliferation. However, the physiological function of this less abundant β-isoform in the islet, and in diabetes, is largely unknown. The aims of the present study, therefore, were to determine how diabetes affects ChREBP-β and elucidate its physiological role in pancreatic beta cells...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27899417/emerging-roles-of-glis3-in-neonatal-diabetes-type-1-and-type-2-diabetes
#8
Xianjie Wen, Yisheng Yang
GLI-similar 3 (GLIS3), a member of the Krüppel-like zinc finger protein subfamily, is predominantly expressed in the pancreas, thyroid, and kidney. Glis3 mRNA can be initially detected in mouse pancreas at embryonic day 11.5 and is largely restricted to β cells, pancreatic polypeptide-expressing cells, as well as ductal cells at later stage of pancreas development. Mutations in GLIS3 cause a neonatal diabetes syndrome, characterized by neonatal diabetes, congenital hypothyroidism, and polycystic kidney. Importantly, genome-wide association studies showed that variations of GLIS3 are strongly associated with both type 1 diabetes (T1D) and type 2 diabetes (T2D) in multiple populations...
November 29, 2016: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27894787/safety-and-efficacy-of-liraglutide-treatment-in-japanese-type-2-diabetes-patients-after-acute-myocardial-infarction-a-non-randomized-interventional-pilot-trial
#9
Masataka Kajiwara, Atsushi Tanaka, Tomohiro Kawasaki, Koichi Nakao, Tomohiro Sakamoto, Shigeru Toyoda, Teruo Inoue, Nobuhiko Koga, Koichi Node
BACKGROUND: Glucagon-like peptide 1 analogs are expected to exert a cardio-protective action due to their effective glucose-lowering action and favorable potency on multifactorial metabolic pathways. However, the safety and tolerability of liraglutide treatment after a recent acute coronary syndrome (ACS) in Japanese patients with type 2 diabetes mellitus (T2DM) have yet to be fully established. METHODS: A total of eight T2DM patients were recruited within 2 weeks after the onset of a ST-elevation myocardial infarction (STEMI) followed by successful percutaneous coronary intervention (PCI)...
November 25, 2016: Journal of Cardiology
https://www.readbyqxmd.com/read/27892930/an-optimized-protocol-for-purification-of-functional-islets-of-langerhans
#10
Youakim Saliba, Jules-Joel Bakhos, Tarek Itani, Nassim Farès
Islets of Langerhans and β-cell isolation constitute routinely used cell models for diabetic research, and refining islet isolation protocols and cell quality assessment is a high priority. Numerous protocols have been published describing isolate of islets, but often rigorous and systematic assessment of their integrity is lacking. Herein, we propose a new protocol for optimal generation of islets. Pancreases from mice and rats were excised and digested using a low-activity collagenase solution and islets were then purified by a series of sedimentations and a Percoll gradient...
November 28, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27892782/c1858t-polymorphism-of-protein-tyrosine-phosphatase-non-receptor-type-22-ptpn22-an-eligible-target-for-prevention-of-type-1-diabetes
#11
Giovanni Prezioso, Laura Comegna, Concetta Di Giulio, Simone Franchini, Francesco Chiarelli, Annalisa Blasetti
In type 1 diabetes (T1D), several genetic factors are associated to β-cell autoimmunity onset and clinical progression. HLA-genes play a major role in susceptibility and initiation of β-cell autoimmunity, whereas non-HLA genes may influence the destruction rate. Areas covered: Our review focuses on the possible role of the PTPN22 C1858T variant as a prognostic factor, given its influence on disease variability. Moreover, we present the potential role of C1858T as a target for tertiary prevention trials and new therapeutic strategies, such as the LYP inhibitors...
November 28, 2016: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/27891128/immune-imbalances-in-non-alcoholic-fatty-liver-disease-from-general-biomarkers-and-neutrophils-to-interleukin-17-axis-activation-and-new-therapeutic-targets
#12
REVIEW
Feliciano Chanana Paquissi
Non-alcoholic fatty liver disease (NAFLD) is an increasing problem worldwide and is associated with negative outcomes such as cirrhosis, hepatocellular carcinoma, insulin resistance, diabetes, and cardiovascular events. Current evidence shows that the immune response has an important participation driving the initiation, maintenance, and progression of the disease. So, various immune imbalances, from cellular to cytokines levels, have been studied, either for better compression of the disease pathophysiology or as biomarkers for severity assessment and outcome prediction...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27890939/the-metal-face-of-protein-tyrosine-phosphatase-1b
#13
REVIEW
Elisa Bellomo, Kshetrimayum Birla Singh, Alberto Massarotti, Christer Hogstrand, Wolfgang Maret
A new paradigm in metallobiochemistry describes the activation of inactive metalloenzymes by metal ion removal. Protein tyrosine phosphatases (PTPs) do not seem to require a metal ion for enzymatic activity. However, both metal cations and metal anions modulate their enzymatic activity. One binding site is the phosphate binding site at the catalytic cysteine residue. Oxyanions with structural similarity to phosphate, such as vanadate, inhibit the enzyme with nanomolar to micromolar affinities. In addition, zinc ions (Zn(2+)) inhibit with picomolar to nanomolar affinities...
November 15, 2016: Coordination Chemistry Reviews
https://www.readbyqxmd.com/read/27890702/foxos-in-the-impaired-heart-new-therapeutic-targets-for-cardiac-diseases
#14
REVIEW
Zhenlong Xin, Zhiqiang Ma, Shuai Jiang, Dongjin Wang, Chongxi Fan, Shouyin Di, Wei Hu, Tian Li, Junjun She, Yang Yang
Cardiac diseases have a high morbidity and mortality and affect the global population. Based on recent accumulating evidence, Forkhead box O (FOXOs) play important roles in cardiac diseases. Therefore, a summary of the current literature on the molecular mechanisms and roles of FOXOs in the heart will provide valuable information. In this review, we first briefly introduce the molecular features of FOXOs. Then, we discuss the regulation and cardiac actions of the FOXO pathways. Based on this background, we expand our discussion to the roles of FOXOs in several major cardiac diseases, such as ischemic cardiac diseases, diabetic cardiomyopathy and myocardial hypertrophy...
November 24, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27889702/statins-and-the-cholesterol-mortality-paradox
#15
José Pedro L Nunes
Large-scale randomised controlled trials, carried out in the context of secondary cardiovascular prevention, have shown that statins are superior to placebo: these drugs were shown to decrease cardiovascular events and total mortality. A further set of clinical trials compared high intensity to low/standard intensity LDL cholesterol lowering in the same setting (using either statins or a statin/ezetimibe association). In this case, a decrease in LDL cholesterol and a concomitant significant reduction in cardiovascular events were seen with intensive therapy, however with no change in total mortality...
November 26, 2016: Scottish Medical Journal
https://www.readbyqxmd.com/read/27887947/berberine-enhances-the-ampk-activation-and-autophagy-and-mitigates-high-glucose-induced-apoptosis-of-mouse-podocytes
#16
Yingli Jin, Shuping Liu, Qingshan Ma, Dong Xiao, Li Chen
High glucose concentration can induce injury of podocytes and berberine has a potent activity against diabetic nephropathy. However, whether and how berberine can inhibit high glucose-mediated injury of podocytes have not been clarified. This study tested the effect of berberine on high glucose-mediated apoptosis and the AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) activation and autophagy in podocytes. The results indicated that berberine significantly mitigated high glucose-decreased cell viability, and nephrin and podocin expression as well as apoptosis in mouse podocytes...
November 22, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27884312/management-of-patients-with-diabetes-and-ckd-%C3%A2-conclusions-from-a-kidney-disease-improving-global-outcomes-kdigo-controversies-conference
#17
Vlado Perkovic, Rajiv Agarwal, Paola Fioretto, Brenda R Hemmelgarn, Adeera Levin, Merlin C Thomas, Christoph Wanner, Bertram L Kasiske, David C Wheeler, Per-Henrik Groop
The prevalence of diabetes around the world has reached epidemic proportions and is projected to increase to 642 million people by 2040. Diabetes is already the leading cause of end-stage kidney disease (ESKD) in most developed countries, and the growth in the number of people with ESKD around the world parallels the increase in diabetes. The presence of kidney disease is associated with a markedly elevated risk of cardiovascular disease and death in people with diabetes. Several new therapies and novel investigational agents targeting chronic kidney disease patients with diabetes are now under development...
December 2016: Kidney International
https://www.readbyqxmd.com/read/27884303/aberrant-mtorc1-activation-kills-tubular-cells-by-inactivating-mir148b-3p
#18
Ken Inoki
A new study by Kuwagata et al. now shows that aberrant activation of the mechanistic target of rapamycin complex 1 in renal tubular cells causes their injury and cell death by enhancing endoplasmic reticulum stress and cell death pathway under diabetic conditions. The study has revealed a novel molecular mechanism in which mechanistic target of rapamycin complex 1 stimulates the tumor necrosis factor signaling by attenuating miR-148b-3p, thereby deteriorating renal tubular cell dysfunction under diabetic conditions...
December 2016: Kidney International
https://www.readbyqxmd.com/read/27878566/pharmacokinetic-and-pharmacodynamic-properties-of-faster-acting-insulin-aspart-versus-insulin-aspart-across-a-clinically-relevant-dose-range-in-subjects-with-type-1-diabetes-mellitus
#19
Tim Heise, Kirstine Stender-Petersen, Ulrike Hövelmann, Jacob Bonde Jacobsen, Leszek Nosek, Eric Zijlstra, Hanne Haahr
BACKGROUND: Absorption of current rapid-acting insulins is too slow for patients with diabetes mellitus to achieve optimal postprandial glucose control. Faster-acting insulin aspart (faster aspart) is insulin aspart in a new formulation with faster early absorption. We compared the pharmacokinetic/pharmacodynamic properties of faster aspart and insulin aspart across a clinically relevant dose range. METHODS: In this randomised, double-blind, crossover trial, 46 subjects with type 1 diabetes mellitus received single subcutaneous doses of faster aspart and insulin aspart at 0...
November 22, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27875339/apolipoprotein-ciii-is-a-new-player-in-diabetes
#20
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
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