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https://www.readbyqxmd.com/read/27921429/-congenital-hyperinsulinism-loss-of-b-cell-self-control
#1
Jan Lebl, Klára Roženková, Štěpánka Průhová
Congenital hyperinsulinism is a serious blood glucose regulation defect that interferes with brain development, leading to mental retardation, neurological sequelae and secondary epilepsy and ultimately may be life-threatening. Congenital hyperinsulinism (CHI) is caused by genetic defects of regulation of insulin secretion that induce insulin oversecretion in intrauterine life and postnatally. The clinical consequence is fetal macrosomia and subsequently neonatal and infantile hypoglycaemia. The most severe form is caused by biallelic mutations of KCNJ11 and ABCC8 genes that encode both potassium channel subunits, whereas their heterozygous mutations as well as enzymatic defects (GLUD1, HADH, GCK) lead to milder presentation...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27920090/islet-derived-cd4-t-cells-targeting-proinsulin-in-human-autoimmune-diabetes
#2
Aaron W Michels, Laurie G Landry, Kristen A McDaniel, Liping Yu, Martha Campbell-Thompson, William W Kwok, Kenneth L Jones, Peter A Gottlieb, John W Kappler, Qizhi Tang, Bart O Roep, Mark A Atkinson, Clayton E Mathews, Maki Nakayama
Type 1 diabetes results from chronic autoimmune destruction of insulin-producing beta cells within pancreatic islets. While insulin is a critical self-antigen in animal models of autoimmune diabetes, due to extremely limited access to pancreas samples, little is known about human antigenic targets for islet-infiltrating T-cells. Here we show that proinsulin peptides are targeted by islet-infiltrating T-cells from type 1 diabetes patients. We identified hundreds of T-cells from inflamed pancreatic islets of three young type 1 diabetes organ donors with a short disease duration with high risk HLA genes using a direct T-cell receptor (TCR) sequencing approach without long-term cell culture...
December 5, 2016: Diabetes
https://www.readbyqxmd.com/read/27919468/somatic-gnaq-mutation-is-enriched-in-brain-endothelial-cells-in%C3%A2-sturge-weber-syndrome
#3
Lan Huang, Javier A Couto, Anna Pinto, Sanda Alexandrescu, Joseph R Madsen, Arin K Greene, Mustafa Sahin, Joyce Bischoff
BACKGROUND: Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder characterized by facial and extracraniofacial capillary malformations and capillary-venule malformations in the leptomeninges. A somatic mosaic mutation in GNAQ (c.548G>A; p.R183Q) was found in SWS brain and skin capillary malformations. Our laboratory showed endothelial cells in skin capillary malformations are enriched for the GNAQ mutation. The purpose of this study is to determine whether the GNAQ mutation is also enriched in endothelial cells in affected SWS brain...
October 21, 2016: Pediatric Neurology
https://www.readbyqxmd.com/read/27918974/generational-change-in-fasting-glucose-and-insulin-among-children-at-ages-5-16y-modelled-on-the-earlybird-study-2015-and-uk-growth-standards-1990-earlybird-69
#4
Mohammod Mostazir, Alison Jeffery, Linda Voss, Terence Wilkin
AIM: Pre-diabetes is a state of beta-cell stress caused by excess demand for insulin. Body mass is an important determinant of insulin demand, and BMI has risen substantially over recent time. We sought to model changes in the parameters of glucose control against rising BMI over the past 25years. METHODS: Using random coefficient mixed models, we established the correlations between HbA1C, fasting glucose, fasting insulin, HOMA2-IR and BMI in contemporary (2015) children (N=307) at ages 5-16y from the EarlyBird study, and modelled their corresponding values 25years ago according to the distribution of BMI in the UK Growth Standards (1990)...
November 28, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/27914732/interaction-of-sex-steroid-hormones-and-obesity-on-insulin-resistance-and-type-2-diabetes-in-men-the-third-national-health-and-nutrition-examination-survey
#5
Ji Li, Hong Lai, Shaoguang Chen, Hong Zhu, Shenghan Lai
AIMS: We examined interaction of sex steroid hormones and obesity with regard to insulin resistance (IR) and type 2 diabetes (T2D) by using nationally representative data from the US. METHODS: Data of 1461 men aged ≥20years who participated in the Third National Health and Nutrition Examination Survey were analyzed. Multiplicative interaction was calculated by cross-product interaction terms in multivariable logistic regression models. Additive interaction was assessed by the relative excess risk due to interaction (RERI)...
October 22, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27914538/adaptive-response-of-rat-pancreatic-%C3%AE-cells-to-insulin-resistance-induced-by-monocrotophos-biochemical-evidence
#6
Raju Nagaraju, Padmanabhan Sharda Rajini
Our previous findings clearly suggested the role of duration of exposure to monocrotophos (MCP) in the development of insulin resistance. Rats exposed chronically to MCP developed insulin resistance with hyperinsulinemia without overt diabetes. In continuation of this vital observation, we sought to delineate the biochemical mechanisms that mediate heightened pancreatic β-cell response in the wake of MCP-induced insulin resistance in rats. Adult rats were orally administered (0.9 and 1.8mg/kgb.w/d) MCP for 180days...
November 2016: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/27912197/rac1-nadph-oxidase-signaling-promotes-cd36-activation-under-glucotoxic-conditions-in-pancreatic-beta-cells
#7
Suma Elumalai, Udayakumar Karunakaran, In Kyu Lee, Jun Sung Moon, Kyu Chang Won
We recently reported that cluster determinant 36 (CD36), a fatty acid transporter, plays a pivotal role in glucotoxicity-induced β-cell dysfunction. However, little is known about how glucotoxicity influences CD36 expression. Emerging evidence suggests that the small GTPase Rac1 is involved in the pathogenesis of beta cell dysfunction in type 2 diabetes (T2D). The primary objective of the current study was to determine the role of Rac1 in CD36 activation and its impact on β-cell dysfunction in diabetes mellitus...
November 23, 2016: Redox Biology
https://www.readbyqxmd.com/read/27912129/incidence-of-complications-in-young-onset-diabetes-comparing-type-2-with-type-1-the-young-diab-study
#8
Anandakumar Amutha, Ranjit Mohan Anjana, Ulagamathesan Venkatesan, Harish Ranjani, Ranjit Unnikrishnan, K M Venkat Narayan, Viswanathan Mohan, Mohammed K Ali
BACKGROUND: There is little data on the incidence of diabetes complications in young onset type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in non European populations. METHODS: From a tertiary diabetes centre, Chennai, India, we recruited 108 T1DM (defined by abrupt onset of symptoms or diabetic ketoacidosis, absent insulin reserve requiring insulin treatment) and 90 T2DM participants (defined by absence of ketosis, good beta-cell reserve, and good response to oral agents) who were diagnosed between the ages of 10 and 25years, and without any evidence of diabetes complications at diagnosis...
November 17, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/27911611/the-influence-of-gh-treatment-on-glucose-homeostasis-in-girls-with-turner-syndrome-a-7-years-study
#9
Federico Baronio, Laura Mazzanti, Ylenia Girtler, Federica Tamburrino, Fiorenzo Lupi, Silvia Longhi, Antonio Fanolla, Giorgio Radetti
CONTEXT: Growth hormone (GH) influences glucose homeostasis mainly by negatively affecting insulin sensitivity. OBJECTIVE: to longitudinally study the insulin sensitivity (HOMA-S), insulin secretion (insulinogenic index - IGI) and capacity of beta cells to adapt to changes in insulin sensitivity (oral disposition index-ODI) in girls affected by Turner syndrome (TS) undergoing GH treatment. DESIGN: a longitudinal retrospective seven years study Setting: a tertiary pediatric endocrine unit and a University pediatric Clinic...
December 2, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27909574/characterization-of-5-2-18-f-fluoroethoxy-l-tryptophan-for-pet-imaging-of-the-pancreas
#10
Ahmed Abbas, Christine Beamish, Rebecca McGirr, John Demarco, Neil Cockburn, Dawid Krokowski, Ting-Yim Lee, Michael Kovacs, Maria Hatzoglou, Savita Dhanvantari
Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2- (18)F-fluoroethoxy)-L-tryptophan ( (18)F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. Procedures: Uptake of (18)F-L-FEHTP was determined in wild-type C57BL/6 mice by ex vivo biodistribution...
2016: F1000Research
https://www.readbyqxmd.com/read/27907006/prediction-of-impending-type-1-diabetes-through-automated-dual-label-measurement-of-proinsulin-c-peptide-ratio
#11
Annelien Van Dalem, Simke Demeester, Eric V Balti, Bart Keymeulen, Pieter Gillard, Bruno Lapauw, Christophe De Block, Pascale Abrams, Eric Weber, Ilse Vermeulen, Pieter De Pauw, Daniël Pipeleers, Ilse Weets, Frans K Gorus
BACKGROUND: The hyperglycemic clamp test, the gold standard of beta cell function, predicts impending type 1 diabetes in islet autoantibody-positive individuals, but the latter may benefit from less invasive function tests such as the proinsulin:C-peptide ratio (PI:C). The present study aims to optimize precision of PI:C measurements by automating a dual-label trefoil-type time-resolved fluorescence immunoassay (TT-TRFIA), and to compare its diagnostic performance for predicting type 1 diabetes with that of clamp-derived C-peptide release...
2016: PloS One
https://www.readbyqxmd.com/read/27906553/short-adult-stature-predicts-impaired-beta-cell-function-insulin-resistance-glycemia-and-type-2-diabetes-in-finnish-men
#12
Jagadish Vangipurapu, Alena Stančáková, Raimo Jauhiainen, Johanna Kuusisto, Markku Laakso
CONTEXT: Recent studies have highlighted the role of height in complex diseases but conflicting information has been reported on height as a predictor of changes in glycemia and risk of type 2 diabetes. OBJECTIVE: Our aim was to investigate the association of height with insulin sensitivity, insulin secretion, glycemia, type 2 diabetes and cardiovascular disease in a large prospective population-based study. DESIGN: The study included 8,746 Finnish men (mean±SD, age 57...
December 1, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27904615/the-effect-of-flaxseed-powder-on-insulin-resistance-indices-and-blood-pressure-in-prediabetic-individuals-a-randomized-controlled-clinical-trial
#13
Afrooz Javidi, Hassan Mozaffari-Khosravi, Azadeh Nadjarzadeh, Ali Dehghani, Mohammad Hassan Eftekhari
BACKGROUND: Designing the effective and early interventions can prevent progression of prediabetes to diabetes. Few studies have shown the effect of flaxseed on glycemic control. This study aimed to assess the effect of flaxseed powder on insulin resistance (IR) indices and blood pressure in prediabetic individuals. MATERIALS AND METHODS: In a randomized clinical trial, 99 prediabetic individuals were randomly divided into three groups: two groups received 40 g (FG40) and 20 g (FG20) flaxseed powder daily for 12 weeks and the third group was the control (CG)...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/27904554/effect-of-helicobacter-pylori-eradication-on-insulin-resistance-among-prediabetic-patients-a-pilot-study-and-single-blind-randomized-controlled-clinical-trial
#14
Ali Kachuei, Masoud Amini, Vahid Sebghatollahi, Awat Feizi, Pooria Hamedani, Bijan Iraj
BACKGROUND: Type II diabetes mellitus (T2DM) is the prevalent type of diabetes in the world. Prediabetic patients are the most probable group to get diabetes. Several studies have mentioned the role of inflammation in the incidence of diabetes. The origin of inflammation can be infection such as Helicobacter pylori (HP) infection. This study was designed to explore the effect of HP eradication on insulin resistance. MATERIALS AND METHODS: This single-blind randomized controlled clinical trial was conducted in 2014-2015...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/27903221/in-vitro-generated-mesenchymal-stem-cells-suitable-tools-to-target-insulin-dependent-diabetes-mellitus
#15
Shruti D Dave, Patel C N, Patel J V, Thakkar U G
A synergy of a pre-accumulated genes with an autoimmunity advancing to slow abolition of pancreatic beta-cells causes insulin deficiency and results enrooting insulin dependent diabetes mellitus (IDDM). As per WHO data worldwide about 150 million people are diabetic and the number may rise to more than double by the year 2025. Any absolute cure for IDDM is not available yet, and one of the credible advent in the field include cell-based therapy. At this conjecture, mesenchymal stem cells (MSC) seems to have a specific and beneficial characteristics due to their in vivo as well as in vitro potential to mimic a pancreatic endocrine phenotype and immune-regulatory actions...
November 21, 2016: Current Stem Cell Research & Therapy
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
#16
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/27899481/hznt8-slc30a8-transgenic-mice-which-overexpress-the-r325w-polymorph-have-reduced-islet-zn2-and-proinsulin-levels-increased-glucose-tolerance-after-a-high-fat-diet-and-altered-levels-of-pancreatic-zinc-binding-proteins
#17
Li Li, Shi Bai, Christian T Sheline
Zinc is involved in both type-1 (T1DM) and type-2 (T2DM) diabetes. The wildtype (WT) form of the beta-cell specific Zn(2+) transporter, ZNT8, is linked to T2DM susceptibility. ZnT8 null mice have a mild phenotype with a slight decrease in glucose tolerance, whereas patients with the ZnT8 R325W polymorphism (rs13266634) have decreased proinsulin staining and susceptibility to T2DM. We measured zinc, insulin, and proinsulin stainings, and IPGTT in transgenic mice overexpressing hZnT8 WT or hZnT8 R325W fed a normal or high fat diet (HFD)...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27899308/insight-gained-from-genome-wide-interaction-and-enrichment-analysis-on-weight-gain-during-citalopram-treatment
#18
Henrik Thyge Corfitsen, Antonio Drago
Weight gain is a possible side effect of the pharmacological antidepressant treatments. Defining antidepressant prescriptions based on personal genetic makeups would decrease the risk of weight gain and increase the quality of the current antidepressant pharmacological treatments. 643 depressed, citalopram treated individuals with available clinical and genome-wide genetic information were investigated to identify the molecular pathways associated with weight gain. 111 individuals experienced weight gain during citalopram treatment...
November 27, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27896979/genome-wide-interaction-with-selected-type-2-diabetes-loci-reveals-novel-loci-for-type-2-diabetes-in-african-americans
#19
Jacob M Keaton, Jacklyn N Hellwege, Maggie C Y Ng, Nicholette D Palmer, James S Pankow, Myriam Fornage, James G Wilson, Adolfo Correa, Laura J Rasmussen-Torvik, Jerome I Rotter, Yii-DER I Chen, Kent D Taylor, Stephen S Rich, Lynne E Wagenknecht, Barry I Freedman, Donald W Bowden
Type 2 diabetes (T2D) is the result of metabolic defects in insulin secretion and insulin sensitivity, yet most T2D loci identified to date influence insulin secretion. We hypothesized that T2D loci, particularly those affecting insulin sensitivity, can be identified through interaction with known T2D loci implicated in insulin secretion. To test this hypothesis, single nucleotide polymorphisms (SNPs) nominally associated with acute insulin response to glucose (AIRg), a dynamic measure of first-phase insulin secretion, and previously associated with T2D in genome-wide association studies (GWAS) were identified in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS; n=492 subjects)...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27894404/streptozotocin-induces-neurite-outgrowth-via-pi3k-akt-and-glycogen-synthase-kinase-3%C3%AE-in-neuro2a-cells
#20
T Nishimoto, R Kimura, A Matsumoto, H Sugimoto
Streptozotocin (STZ), a naturally occurring chemical, is toxic to the various kinds of cells such as insulin-producing beta cells. However, the beneficial effect of STZ on neuronal cells such as neurite outgrowth-inducing activity has been unknown. In this study, we examined the effect of STZ on neurite outgrowth in mouse neuronal Neuro2a cells. STZ (0.01 mM~5 mM) exerted remarkable neurite outgrowth-inducing activity in Neuro2a cells in a concentration dependent manner. STZ also had the same neurite outgrowth-inducing activity as that of retinoic acid (RA), which is well known neurite outgrowth inducer...
October 31, 2016: Cellular and Molecular Biology
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