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Impaired glucose regulation

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https://www.readbyqxmd.com/read/29466436/loss-of-hcn2-leads-to-delayed-gastrointestinal-motility-and-reduced-energy-intake-in-mice
#1
Daniel W Fisher, Phillip Luu, Neha Agarwal, Jonathan E Kurz, Dane M Chetkovich
Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels are important regulators of excitability in neural, cardiac, and other pacemaking cells, which are often altered in disease. In mice, loss of HCN2 leads to cardiac dysrhythmias, persistent spike-wave discharges similar to those seen in absence epilepsy, ataxia, tremor, reduced neuropathic and inflammatory pain, antidepressant-like behavior, infertility, and severely restricted growth. While many of these phenotypes have tissue-specific mechanisms, the cause of restricted growth in HCN2 knockout animals remains unknown...
2018: PloS One
https://www.readbyqxmd.com/read/29460080/heterogeneity-of-gestational-diabetes-gdm-and-long-term-risk-of-diabetes-and-metabolic-syndrome-findings-from-the-radiel-study-follow-up
#2
Emilia Huvinen, Johan G Eriksson, Saila B Koivusalo, Nora Grotenfelt, Aila Tiitinen, Beata Stach-Lempinen, Kristiina Rönö
AIMS: To assess the metabolic health of obese and non-obese women at high GDM risk 5 years postpartum. METHODS: This is a secondary analysis of the 5-year follow-up of the RADIEL GDM prevention study including 333 women at high GDM risk (BMI ≥ 30 kg/m2 and/or previous GDM). Five years postpartum metabolic health was assessed including anthropometric measurements, oral glucose tolerance test, lipid metabolism, and body composition as well as medical history questionnaires...
February 19, 2018: Acta Diabetologica
https://www.readbyqxmd.com/read/29458148/untimely-oxidative-stress-in-%C3%AE-cells-leads-to-diabetes-role-of-circadian-clock-in-%C3%AE-cell-function
#3
REVIEW
J Lee, K Ma, M Moulik, V Yechoor
Diabetes results from a loss of β-cell function. With the number of people with diabetes reaching epidemic proportions globally, understanding mechanisms that are contributing to this increasing prevalence is critical. One such factor has been circadian disruption, with shift-work, light pollution, jet-lag, increased screen time, all acting as potential contributory factors. Though circadian disruption has been epidemiologically associated with diabetes and other metabolic disorders for many decades, it is only recently that there has been a better understanding of the underlying molecular mechanisms...
February 16, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29457786/intracellular-lipid-metabolism-impairs-%C3%AE-cell-compensation-during-diet-induced-obesity
#4
Risheng Ye, Ruth Gordillo, Mengle Shao, Toshiharu Onodera, Zhe Chen, Shiuhwei Chen, Xiaoli Lin, Jeffrey A SoRelle, Xiaohong Li, Miao Tang, Mark P Keller, Regina Kuliawat, Alan D Attie, Rana K Gupta, William L Holland, Bruce Beutler, Joachim Herz, Philipp E Scherer
The compensatory proliferation of insulin-producing β cells is critical to maintaining glucose homeostasis at the early stage of type 2 diabetes. Failure of β cells to proliferate results in hyperglycemia and insulin dependence in patients. To understand the effect of the interplay between β cell compensation and lipid metabolism upon obesity and peripheral insulin resistance, we eliminated LDL receptor-related protein 1 (LRP1), a pleiotropic mediator of cholesterol, insulin, energy metabolism, and other cellular processes, in β cells...
February 19, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29455245/chronic-hyperinsulinemia-induced-mir-27b-is-linked-to-adipocyte-insulin-resistance-by-targeting-insulin-receptor
#5
Ankita Srivastava, Kripa Shankar, Muheeb Beg, Sujith Rajan, Abhishek Gupta, Salil Varshney, Durgesh Kumar, Sanchita Gupta, Raj Kumar Mishra, Anil Nilkanth Gaikwad
Defect in insulin signaling leads to the development of insulin resistance followed by type 2 diabetes. Exploiting our previously developed physiological chronic hyperinsulinemia (CI)-mediated insulin resistance (IR) model, we wanted to understand how miRNAs contribute to the development of IR. Amongst the identified and validate miRNAs, the expression of miR-27b was found to be highly upregulated during CI-induced IR in 3T3-L1 adipocytes. We also validated the expression of miR-27b in CI-induced IR in human mesenchymal stem cell (hMSC)-derived adipocytes and in vivo high fat diet (HFD)-induced IR mice model...
February 17, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29453918/high-dose-of-histone-deacetylase-inhibitors-affects-insulin-secretory-mechanism-of-pancreatic-beta-cell-line
#6
Eiji Yamato
OBJECTIVE: Histone deacytylase inhibitors (HDACis) inhibit the deacetylation of the lysine residue of proteins, including histones, and regulate the transcription of a variety of genes. Recently, HDACis have been used clinically as anti-cancer drugs and possible anti-diabetic drugs. Even though HDACis have been proven to protect the cytokine-induced damage of pancreatic beta cells, evidence also shows that high doses of HDACis are cytotoxic. In the present study, we, therefore, investigated the eff ect of HDACis on insulin secretion in a pancreatic beta cell line...
January 1, 2018: Endocrine Regulations
https://www.readbyqxmd.com/read/29452132/effect-of-the-gstm1-gene-deletion-on-glycemic-variability-sympatho-vagal-balance-and-arterial-stiffness-in-patients-with-metabolic-syndrome-but-without-diabetes
#7
Andrea Iorio, Dorina Ylli, Renato Polimanti, Fabiana Picconi, Paola Maggio, Davide Francomano, Antonio Aversa, Dario Manfellotto, Maria Fuciarelli, Simona Frontoni
AIMS: An increased rate of cerebrovascular complications in patients with metabolic syndrome (MetS) has been reported. Previous studies demonstrated an association between glycemic variability (GV) and cerebrovascular reactivity (CRV) in MetS, thus suggesting a putative role of GV on cerebrovascular events. Although the pathophysiological mechanism linking GV to damage is still to be elucidated, evidence suggests oxidative stress plays a crucial role. Since functional variants in glutathione S-transferases (GST) genes modulate the cellular detoxification processes, the aim of this study was to elucidate the involvement of GSTs in MetS and investigating the correlation with GV, arterial stiffness, and sympatho-vagal (SV) balance...
February 13, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29451141/associations-between-body-composition-indices-and-metabolic-disorders-in-chinese-adults-a-cross-sectional-observational-study
#8
Rong Zhang, Sheng-Yong Dong, Fei Wang, Cong Ma, Xiao-Lan Zhao, Qiang Zeng, Ao Fei
Background: Obesity induces dyslipidemia, hypertension, glucose intolerance, and inflammatory state, which results in atherogenic processes, diabetes, and cardiovascular disease. We usually use body composition indices, such as body mass index (BMI), body fat percentage (BFP), waist circumference-height ratio (WHtR), and waist-hip ratio (WHR) to reflect the obesity. The aim of this large population-based cross-sectional study was to investigate the associations between body composition indices and metabolic parameters in Chinese adults...
February 20, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/29449530/the-type-2-diabetes-associated-hmg20a-gene-is-mandatory-for-islet-beta-cell-functional-maturity
#9
Jose M Mellado-Gil, Esther Fuente-Martín, Petra I Lorenzo, Nadia Cobo-Vuilleumier, Livia López-Noriega, Alejandro Martín-Montalvo, Irene de Gracia Herrera Gómez, Maria Ceballos-Chávez, Laura Gómez-Jaramillo, Antonio Campos-Caro, Silvana Y Romero-Zerbo, Júlia Rodríguez-Comas, Joan-Marc Servitja, Gemma Rojo-Martinez, Abdelkrim Hmadcha, Bernat Soria, Marco Bugliani, Piero Marchetti, Francisco J Bérmudez-Silva, Jose C Reyes, Manuel Aguilar-Diosdado, Benoit R Gauthier
HMG20A (also known as iBRAF) is a chromatin factor involved in neuronal differentiation and maturation. Recently small nucleotide polymorphisms (SNPs) in the HMG20A gene have been linked to type 2 diabetes mellitus (T2DM) yet neither expression nor function of this T2DM candidate gene in islets is known. Herein we demonstrate that HMG20A is expressed in both human and mouse islets and that levels are decreased in islets of T2DM donors as compared to islets from non-diabetic donors. In vitro studies in mouse and human islets demonstrated that glucose transiently increased HMG20A transcript levels, a result also observed in islets of gestating mice...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29447934/mismatch-between-gluts-and-glucose-levels-causes-neuronal-damage-during-glucose-fluctuations
#10
Zhichao Xie, Jun Guo, Yan Kang, Xiaofeng Ou
Abnormal glucose levels damage the central nervous system, especially in case of rapid fluctuations. Even a single episode of glucose reperfusion can result in overt impairment of neurons. Oxidative stress plays an important role in this process, sharing properties with the pathophysiologic changes of glucose neurotoxicity. Glucose transporters (GLUTs) located in the brain are involved in direct glucose uptake by neurons. Instead of being insulin-sensitive, these transporters are regulated by glucose levels in the extracellular fluid, increasing their expression while glucose levels fall, to absorb more glucose...
March 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29444430/%C3%AE-cell-specific-deletion-of-the-il-1-receptor-antagonist-impairs-%C3%AE-cell-proliferation-and-insulin-secretion
#11
Marianne Böni-Schnetzler, Stéphanie P Häuselmann, Elise Dalmas, Daniel T Meier, Constanze Thienel, Shuyang Traub, Friederike Schulze, Laura Steiger, Erez Dror, Praxedis Martin, Pedro L Herrera, Cem Gabay, Marc Y Donath
Interleukin-1 receptor antagonist (IL-1Ra) is elevated in the circulation during obesity and type 2 diabetes (T2D) but is decreased in islets from patients with T2D. The protective role of local IL-1Ra was investigated in pancreatic islet β cell (βIL-1Ra)-specific versus myeloid-cell (myeloIL-1Ra)-specific IL-1Ra knockout (KO) mice. Deletion of IL-1Ra in β cells, but not in myeloid cells, resulted in diminished islet IL-1Ra expression. Myeloid cells were not the main source of circulating IL-1Ra in obesity...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29444316/glucose-triggers-stomatal-closure-mediated-by-gin1-gin2-pyr-rcar-ros-no-cdpk6-and-slac1-in-arabidposis
#12
Yan Li, Shanshan Xu, Zhiwei Wang, Lingchao He, Kang Xu, Genxuan Wang
Sugars play important roles in regulating plant growth, development and stomatal movement. Here, we found that glucose triggered stomatal closure, showing a dose-and time-dependent manner in Arabidopsis. Pharmacological data showed that glucose-induced stomatal closure was greatly inhibited by catalase (CAT, a reactive oxygen species (ROS) scavenger), diphenyleneiodonium chloride (DPI, an NADPH oxidase inhibitor), lanthanum chloride (LaCl3, a Ca2+ channel blocker), ethylene glycol tetraacetic acid (EGTA, a Ca2+ chelator), two nitrate reductase (NR) inhibitors, tungstate and sodium azide (NaN3), while not affected by salicylhydroxamic acid (SHAM, a peroxidase inhibitor)...
February 10, 2018: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29442468/the-role-of-pancreatic-polypeptide-in-pancreatic-diseases
#13
REVIEW
Mariola Śliwińska-Mossoń, Grzegorz Marek, Halina Milnerowicz
The aim of this study was to review the diagnostic significance of pancreatic polypeptide (PP) in pancreatic diseases. PP may play a significant role in monitoring the development of the disease and the patient's healing process, particularly after the removal of a portion of the pancreas. Determining PP in acute pancreatitis is quite controversial. At the 1st stage of severe pancreatic damage, there is excessive PP release followed by its fall. In patients with chronic pancreatitis, a significant decrease in PP secretion was found in the presence of a food stimulant...
December 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29435181/hyperglycemia-induced-testicular-damage-in-type-2-diabetes-mellitus-rats-exhibiting-microcirculation-impairments-associated-with-vascular-endothelial-growth-factor-decreased-via-pi3k-akt-pathway
#14
Lingli Long, Han Qiu, Bing Cai, Ningning Chen, Xiaofang Lu, Shuhui Zheng, Xiaoxin Ye, Yubin Li
As an endocrine disease, type 2 diabetes mellitus (T2DM) can cause testicular damage which induces male infertility. However, the underlying mechanism is still not clear. We prove that T2DM induced testicular microcirculation impairment involves the decrease of VEGF and these actions are regulated by PI3K/Akt pathway. In our study, rats were divided into three groups (n=8): control group, diabetes group and diabetes + VEGF group. Intraperitoneal injection of streptozotocin (STZ, 65mg/Kg, at 9th week) and daily high-fat diet were used to establish T2DM rat model...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29432553/short-term-heat-stress-altered-metabolism-and-insulin-signaling-in-skeletal-muscle
#15
Shanthi Ganesan, Corey M Summers, Sarah C Pearce, Nicholas K Gabler, Rudy J Valentine, Lance H Baumgard, Robert P Rhoads, Joshua T Selsby
Heat-related complications continue to be a major health concern for humans and animals and lead to potentially life-threatening conditions. Heat stress (HS) alters metabolic parameters and may alter glucose metabolism and insulin signaling. Therefore, the purpose of this investigation was to determine the extent to which 12 h of HS altered energetic metabolism in oxidative skeletal muscle. To address this, crossbred gilts (n=8/group) were assigned to one of three environmental treatments for 12 h: thermoneutral (TN; 21° C), heat stress (HS; 37° C), or pair-fed to HS counterparts but housed in TN conditions (PFTN)...
February 8, 2018: Journal of Animal Science
https://www.readbyqxmd.com/read/29428063/integrated-model-of-insulin-and-glucose-kinetics-describing-both-hepatic-glucose-and-pancreatic-insulin-regulation
#16
Mogens Erlandsen, Christoffer Martinussen, Claus Højbjerg Gravholt
BACKGROUND AND OBJECTIVES: Modeling of glucose kinetics has to a large extent been based on models with plasma insulin as a known forcing function. Furthermore, population-based statistical methods for parameter estimation in these models have mainly addressed random inter-individual variations and not intra-individual variations in the parameters. Here we present an integrated whole-body model of glucose and insulin kinetics which extends the well-known two-compartment glucose minimal model...
March 2018: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/29423939/human-mait-cells-show-metabolic-quiescence-with-rapid-glucose-dependent-upregulation-of-granzyme-b-upon-stimulation
#17
Madeleine E Zinser, Andrew J Highton, Ayako Kurioka, Barbara Kronsteiner, Joachim Hagel, Tianqi Leng, Emanuele Marchi, Chansavath Phetsouphanh, Chris B Willberg, Susanna J Dunachie, Paul Klenerman
Mucosal-associated invariant T (MAIT) cells are a well-characterized innate-like T cell population abundant in the human liver, peripheral tissues and blood. MAIT cells serve in the first line of defense against infections, through engagement of their T cell receptor, which recognizes microbial metabolites presented on MR1, and through cytokine-mediated triggering. Typically, they show a quiescent memory phenotype but can undergo rapid up-regulation of effector functions including cytolysis upon stimulation...
February 9, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29423494/egcg-evokes-nrf2-nuclear-translocation-and-dampens-ptp1b-expression-to-ameliorate-metabolic-misalignment-under-insulin-resistance-condition
#18
Yashi Mi, Wentong Zhang, Haoyu Tian, Runnan Li, Shuxian Huang, Xingyu Li, Guoyuan Qi, Xuebo Liu
As a major nutraceutical component of green tea (-)-epigallocatechin-3-gallate (EGCG) has attracted interest from scientists due to its well-documented antioxidant and antiobesity bioactivities. In the current study, we aimed to investigate the protective effect of EGCG on metabolic misalignment and in balancing the redox status in mice liver and HepG2 cells under insulin resistance condition. Our results indicated that EGCG accelerates the glucose uptake and evokes IRS-1/Akt/GLUT2 signaling pathway via dampening the expression of protein tyrosine phosphatase 1B (PTP1B)...
February 9, 2018: Food & Function
https://www.readbyqxmd.com/read/29416045/%C3%AE-cell-glucokinase-suppresses-glucose-regulated-glucagon-secretion
#19
Davide Basco, Quan Zhang, Albert Salehi, Andrei Tarasov, Wanda Dolci, Pedro Herrera, Ioannis Spiliotis, Xavier Berney, David Tarussio, Patrik Rorsman, Bernard Thorens
Glucagon secretion by pancreatic α-cells is triggered by hypoglycemia and suppressed by high glucose levels; impaired suppression of glucagon secretion is a hallmark of both type 1 and type 2 diabetes. Here, we show that α-cell glucokinase (Gck) plays a role in the control of glucagon secretion. Using mice with α-cell-specific inactivation of Gck (αGckKO mice), we find that glucokinase is required for the glucose-dependent increase in intracellular ATP/ADP ratio and the closure of KATP channels in α-cells and the suppression of glucagon secretion at euglycemic and hyperglycemic levels...
February 7, 2018: Nature Communications
https://www.readbyqxmd.com/read/29414665/improving-hyperglycemic-effect-of-fgf-21-is-associated-with-alleviating-inflammatory-state-in-diabetes
#20
Nan Wang, Tong-Yu Xu, Xu Zhang, Jun-Yan Li, Yun-Xin Wang, Xiao-Chen Guo, Si-Ming Li, Wen-Fei Wang, De-Shan Li
Type 2 diabetes mellitus (T2DM) is accompanied by abnormal glucose metabolism and low-grade chronic inflammation. Fibroblast growth factor 21 (FGF-21) is a novel metabolic regulator and can function as an endocrine hormone to regulate glucose and lipid metabolism. Recently, FGF-21 was found to have anti-inflammatory effect, to our knowledge, the effect of FGF-21 on inflammatory state in diabetes has not been elucidated. Here, we use db/db mice as a Type 2 diabetes model to determine whether FGF-21 alleviates inflammatory state while improves hyperglycemia...
February 2, 2018: International Immunopharmacology
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