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Diabetes

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https://www.readbyqxmd.com/read/28432188/magnetic-resonance-neurography-visualizes-abnormalities-in-sciatic-and-tibial-nerves-in-patients-with-type-1-diabetes-and-neuropathy
#1
Michael Vaeggemose, Mirko Pham, Steffen Ringgaard, Hatice Tankisi, Niels Ejskjaer, Sabine Heiland, Per L Poulsen, Henning Andersen
This study evaluates whether diffusion-tensor-imaging MR-Neurography (DTI-MRN), T2-relaxation-time and proton-spin-density can detect and grade neuropathic abnormalities in patients with type 1 diabetes.Forty-nine patients with type 1 diabetes (11 with severe polyneuropathy (sDPN), 13 with mild polyneuropathy (mDPN) and 25 without polyneuropathy (nDPN)) and 30 healthy controls (HC) were included. Clinical examinations, nerve-conduction-studies and vibratory-perception-thresholds determined the presence and severity of DPN...
April 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28428225/empagliflozin-and-kinetics-of-renal-glucose-transport-in-healthy-and-type-2-diabetic-individuals
#2
Hussein Al-Jobori, Giuseppe Daniele, Eugenio Cersosimo, Curtis Triplitt, Luke Norton, Ralph A DeFronzo, Muhammad Abdul-Ghani
Renal glucose reabsorption was measured with the stepped-hyperglycemic clamp in 15 T2DM and 15 non-diabetic subjects after 2 days and after more chronic (14 days) treatment with empagliflozin. T2DM patients had significantly greater maximal renal glucose transport (TmG) compared to nondiabetic subjects at baseline (459±53 vs 337±25 mg/min, p<0.05). Empagliflozin treatment for 48 hours reduced the TmG in both diabetic and non-diabetic individuals by 44±7% and 53±6%, respectively (both p<0.001). TmG was further reduced by empagliflozin in both groups on day 14 (by 65±5% and 75±3%, respectively)...
April 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28428224/familial-hypercholesterolemia-and-type-2-diabetes-in-the-old-order-amish
#3
Huichun Xu, Kathleen A Ryan, Thomas J Jaworek, Lorraine Southam, Jeffrey G Reid, John D Overton, Aris Baras, Marja K Puurunen, Eleftheria Zeggini, Simeon I Taylor, Alan R Shuldiner, Braxton D Mitchell
Alleles associated with lower levels of low density lipoprotein cholesterol (LDL-C) have recently been associated with an increased risk of type 2 diabetes (T2D), highlighting the complex relationship between LDL-C and diabetes. This observation begs the question whether LDL-C-raising alleles are associated with a decreased risk of T2D. This issue was recently addressed in a large familial hypercholesterolemia (FH) screening study, which reported a lower prevalence of self-reported diabetes in FH subjects than age-matched relatives without FH...
April 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28424160/heterogeneous-nuclear-ribonucleoprotein-f-stimulates-sirtuin-1-gene-expression-and-attenuates-nephropathy-progression-in-diabetic-mice
#4
Chao-Sheng Lo, Yixuan Shi, Isabelle Chenier, Anindya Ghosh, Chin-Han Wu, Jean-Francois Cailhier, Jean Ethier, Jean-Baptiste Lattouf, Janos G Filep, Julie R Ingelfinger, Shao-Ling Zhang, John S D Chan
We investigated the mechanism of heterogeneous nuclear ribonucleoprotein F (hnRNP F) renoprotective action on a type 2 diabetic (T2D) (db/db) mice. Immortalized rat renal proximal tubular cells (IRPTCs) and human T2D kidneys were also studied. Db/db mice developed hyperglycemia, oxidative stress and nephropathy at age 20 weeks compared to their db/m littermates. These abnormalities, with the exception of hyperglycemia, were attenuated in db/db hnRNP F-transgenic (Tg) mice specifically overexpressing hnRNP F in their RPTCs...
April 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28424159/prolonged-elimination-of-negative-feedback-control-mechanisms-along-the-insulin-signalling-pathway-impairs-%C3%AE-cell-function-in-vivo
#5
Roi Isaac, Yaron Vinik, Sigalit Boura-Halfon, Lydia Farack, Sarina Streim, Eytan Elhanany, Zvi Kam, Yehiel Zick
Cellular stress and pro-inflammatory cytokines induce phosphorylation of insulin receptor substrate (IRS) proteins at Ser sites that inhibit insulin and IGF-1 signalling. We therefore examined the effects of mutation of five 'inhibitory' Ser phosphorylation sites on IRS2 function in transgenic mice that overexpress, selectively in pancreatic β cells, either wild-type (WT) or a mutated IRS2 protein (IRS2(5A)). Islets size, number, and mRNA levels of catalase and superoxide dismutase, were increased, while those of nitric oxide synthase were decreased in 7-10 weeks old IRS2(5A)-β mice compared to IRS2(WT)-β mice...
April 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28420673/a-single-bout-of-high-intensity-interval-training-reduces-awareness-of-subsequent-hypoglycemia-in-patients-with-type-1-diabetes
#6
Hanne M Rooijackers, Evita C Wiegers, Marinette van der Graaf, Dick H Thijssen, Roy P C Kessels, Cees J Tack, Bastiaan E de Galan
High-intensity interval training (HIIT) gains increasing popularity in patients with diabetes. HIIT acutely increases plasma lactate levels. This may be important, since administration of lactate during hypoglycemia suppresses symptoms and counterregulation, whilst preserving cognitive function. We tested the hypothesis that HIIT acutely reduces awareness of hypoglycemia and attenuates hypoglycemia-induced cognitive dysfunction. In a randomized crossover trial, patients with type 1 diabetes and normal awareness of hypoglycemia (NAH), patients with impaired awareness of hypoglycemia (IAH), and healthy participants (n=10 per group) underwent a hyperinsulinemic-hypoglycemic (2...
April 18, 2017: Diabetes
https://www.readbyqxmd.com/read/28416628/impaired-glutamatergic-neurotransmission-in-the-vmh-may-contribute-to-defective-counterregulation-in-recurrently-hypoglycemic-rats
#7
Golam M I Chowdhury, Peili Wang, Alisha Ciardi, Ramanaiah Mamillapalli, Justin Johnson, Wanling Zhu, Tore Eid, Kevin Behar, Owen Chan
The objectives of this study were to understand the role of ventromedial hypothalamic (VMH) glutamatergic neurotransmission in response to hypoglycemia and to elucidate the effects of recurrent hypoglycemia (RH) on this neurotransmitter. We measured 1) changes in interstitial VMH glutamate levels using microdialysis and biosensors, 2) identified the receptors that mediate glutamate's stimulatory effects on the counterregulatory responses, 3) quantified glutamate metabolic enzyme levels in the VMH, 4) examined astrocytic glutamate reuptake mechanisms and 5) used (1)H-[(13)C]-NMR spectroscopy to evaluate the effects of RH on neuronal glutamate metabolism...
April 17, 2017: Diabetes
https://www.readbyqxmd.com/read/28411267/nfe2-induces-mir-423-5p-to-promote-gluconeogenesis-and-hyperglycemia-by-repressing-hepatic-fam3a-atp-akt-pathway
#8
Weili Yang, Junpei Wang, Zhenzhen Chen, Ji Chen, Yuhong Meng, Liming Chen, Yongsheng Chang, Bin Geng, Libo Sun, Lin Dou, Jian Li, Youfei Guan, Qinghua Cui, Jichun Yang
Under obese condition, hepatic FAM3A expression is repressed, but the underlying mechanism remains unknown. This study determined the role and mechanism of miR-423-5p in hepatic glucose and lipid metabolism by repressing FAM3A expression. miR-423-5p expression was increased in the livers of obese diabetic mice and NAFLD patients with decreased FAM3A expression. miR-423-5p directly targeted FAM3A mRNA to repress its expression and FAM3A-ATP-Akt pathway in cultured hepatocytes. Hepatic miR-423-5p inhibition suppressed gluconeogenesis, and improved insulin resistance, hyperglycemia and fatty liver in obese diabetic mice...
April 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28411266/genetic-variation-at-the-sulfonylurea-receptor-type-2-diabetes-and-coronary-heart-disease
#9
Connor A Emdin, Derek Klarin, Pradeep Natarajan, Jose C Florez, Sekar Kathiresan, Amit V Khera
Despite widespread clinical use in the treatment of type 2 diabetes, the impact of sulfonylurea therapy on cardiovascular outcomes remains uncertain. Studies of naturally occurring genetic variation can be used to anticipate the expected clinical consequences of a pharmacologic therapy. A common missense variant in the gene encoding a component of the sulfonylurea receptor (ABCC8 p.A1369S) promotes closure of the target channel of sulfonylurea therapy and is associated with increased insulin secretion, thus mimicking the effects of sulfonylurea therapy...
April 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28408435/neurturin-and-a-glp-1-analogue-act-synergistically-to-alleviate-diabetes-in-zucker-diabetic-fatty-rats
#10
James L Trevaskis, Chester Bittencourt Sacramento, Hani Jouihan, Safina Ali, John Le Lay, Stephanie Oldham, Nicholas Bhagroo, Brandon B Boland, Jennifer Cann, Yuan Chang, Terrence O'Day, Victor Howard, Christina Reers, Maria Sorhede Winzell, David M Smith, Michael Feigh, Pernille Barkholt, Kay Schreiter, Matthias Austen, Uwe Andag, Simon Thompson, Lutz Jermutus, Matthew P Coghlan, Joseph Grimsby, Cord Dohrmann, Christopher J Rhodes, Cristina M Rondinone, Arun Sharma
Neurturin (NRTN), a member of the glial-derived neurotrophic factor (GDNF) family, was identified from an embryonic chicken pancreatic cDNA library in a screen for secreted factors. Here, we assessed the potential antidiabetic activities of NRTN relative to liraglutide, a GLP-1 receptor agonist, in Zucker diabetic fatty (ZDF) rats. Subcutaneous administration of NRTN to 8-week-old male ZDF rats prevented the development of hyperglycemia and improved metabolic parameters similar to liraglutide. NRTN treatment increased pancreatic insulin content and β-cell mass, and prevented deterioration of islet organization...
April 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28408434/renal-and-vascular-effects-of-uric-acid-lowering-in-normouricemic-patients-with-uncomplicated-type-1-diabetes
#11
Yuliya Lytvyn, Ronnie Har, Amy Locke, Vesta Lai, Derek Fong, Andrew Advani, Bruce A Perkins, David Z I Cherney
Higher plasma uric acid (PUA) levels are associated with lower GFR and higher blood pressure (BP) in patients with type 1 diabetes (T1D). Our aim was to determine the impact of PUA lowering on renal and vascular function in patients with uncomplicated T1D.T1D patients (n=49) were studied under eu- and hyperglycemic conditions at baseline and after PUA lowering with febuxostat (FBX) for 8 weeks. Healthy controls (HC) were studied under normoglycemic conditions (n=24). PUA, GFR (inulin), effective renal plasma flow (ERPF, paraaminohippurate), BP and hemodynamic responses to an infusion of angiotensin II (assessment of intrarenal RAAS) were measured pre- and post-FBX...
April 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28404597/altered-mirna-29-expression-in-type-2-diabetes-influences-glucose-and-lipid-metabolism-in-skeletal-muscle
#12
Julie Massart, Rasmus J O Sjögren, Leonidas S Lundell, Jonathan M Mudry, Niclas Franck, Donal J O'Gorman, Brendan Egan, Juleen R Zierath, Anna Krook
MicroRNAs have emerged as important regulators of glucose and lipid metabolism in several tissues, however, their role in skeletal muscle remains poorly characterized. We determined the effects of the miR-29 family on glucose and lipid metabolism, and insulin responsiveness in skeletal muscle. We provide evidence that miR-29a and miR-29c are increased in skeletal muscle from type 2 diabetic patients and decreased following endurance training in healthy young men and in rats. In primary human skeletal muscle cells, inhibition and overexpression strategies demonstrate that miR-29a and miR-29c regulate glucose uptake and insulin-stimulated glucose metabolism...
April 12, 2017: Diabetes
https://www.readbyqxmd.com/read/28404596/tumor-necrosis-factor-a-promotes-phosphoinositide-3-kinase-enhancer-a-and-amp-activated-protein-kinase-interaction-to-suppress-lipid-oxidation-in-skeletal-muscle
#13
Margaret Chui Ling Tse, Oana Herlea-Pana, Daniel Brobst, Xiuying Yang, John Wood, Xiang Hu, Zhixue Liu, Chi Wai Lee, Aung Moe Zaw, Billy K C Chow, Keqiang Ye, Chi Bun Chan
Tumor necrosis factor α (TNFα) is an inflammatory cytokine that plays a central role in obesity-induced insulin resistance. It also controls cellular lipid metabolism but the underlining mechanism is poorly understood. We report here that phosphoinositide 3-kinase enhancer A (PIKE-A) is a novel effector of TNFα to facilitate its metabolic modulation in the skeletal muscle. Depletion of PIKE-A in C2C12 myotubes diminished the inhibitory activities of TNFα on mitochondrial respiration and lipid oxidation, whereas PIKE-A overexpression exacerbated these cellular responses...
April 12, 2017: Diabetes
https://www.readbyqxmd.com/read/28400392/identification-of-runx1-as-a-mediator-of-aberrant-retinal-angiogenesis
#14
Jonathan D Lam, Daniel J Oh, Lindsay L Wong, Dhanesh Amarnani, Cindy Park-Windhol, Angie V Sanchez, Jonathan Cardona-Velez, Declan McGuone, Anat O Stemmer-Rachamimov, Dean Eliott, Diane R Bielenberg, Tave van Zyl, Lishuang Shen, Xiaowu Gai, Patricia A D'Amore, Leo A Kim, Joseph F Arboleda-Velasquez
Proliferative diabetic retinopathy (PDR) is a common cause of blindness in the developed world's working adult population, and affects those with type 1 and type 2 diabetes mellitus. We identified Runt-related transcription factor 1 (RUNX1) as a gene upregulated in CD31+ vascular endothelial cells obtained from human PDR fibrovascular membranes (FVM) via transcriptomic analysis. In vitro studies using human retinal microvascular endothelial cells (HRMECs) showed increased RUNX1 RNA and protein expression in response to high glucose whereas RUNX1 inhibition reduced HRMEC migration, proliferation, and tube formation...
April 11, 2017: Diabetes
https://www.readbyqxmd.com/read/28396510/in-vivo-enrichment-of-diabetogenic-t-cells
#15
Martin A Thelin, Stephan Kissler, Frederic Vigneault, Alexander L Watters, Des White, Sandeep T Koshy, Sarah A Vermillion, David J Mooney, Thomas Serwold, Omar A Ali
Dysfunctional T cells can mediate autoimmunity, but the inaccessibility of autoimmune tissues and the rarity of autoimmune T cells in the blood hinder their study. Here, we describe a method to enrich and harvest autoimmune T cells in vivo using a biomaterial scaffold loaded with protein antigens. In model antigen systems, we find that antigen-specific T cells become enriched within scaffolds containing their cognate antigens. When scaffolds containing lysates from an insulin-producing β-cell line were implanted subcutaneously in autoimmune diabetes prone NOD mice, β-cell reactive T cells homed to these scaffolds and became enriched...
April 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28389470/rac1-and-ampk-account-for-the-majority-of-muscle-glucose-uptake-stimulated-by-ex-vivo-contraction-but-not-in-vivo-exercise
#16
Lykke Sylow, Lisbeth L V Møller, Maximilian Kleinert, Gommaar D'Hulst, Estelle De Groote, Peter Schjerling, Gregory R Steinberg, Thomas E Jensen, Erik A Richter
Exercise bypasses insulin resistance to increase glucose uptake in skeletal muscle and therefore represents an important alternative to stimulate glucose uptake in insulin resistant muscle. Both Rac1 and AMPK have been shown to partly regulate contraction-stimulated muscle glucose uptake but whether those two signaling pathways jointly account for the entire signal to glucose transport is unknown. We therefore studied the ability of contraction and exercise to stimulate glucose transport in isolated muscles with AMPK loss-of-function combined with either pharmacological inhibition or genetic deletion of Rac1...
April 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28389469/metabolic-syndrome-insulin-resistance-and-cognitive-dysfunction-does-your-metabolic-profile-affect-your-brain
#17
Jesper S Neergaard, Katrine Dragsbæk, Claus Christiansen, Henning B Nielsen, Susanne Brix, Morten A Karsdal, Kim Henriksen
Dementia and type 2 diabetes are both characterized by long prodromal phases challenging the study of potential risk factors and their temporal relation. The progressive relation between metabolic syndrome, insulin resistance, and dementia has recently been questioned, wherefore the aim of this study was to assess the potential association between these precursors of type 2 diabetes and cognitive dysfunction. Using data from the Prospective Epidemiological Risk Factor study (n=2,103), a prospective study of elderly women in Denmark, we found that impaired fasting plasma glucose was associated with 44% (9%-91%) larger probability of developing cognitive dysfunction...
April 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28385803/insulin-receptor-signaling-in-pomc-but-not-agrp-neurons-controls-adipose-tissue-insulin-action
#18
Andrew C Shin, Nika Filatova, Claudia Lindtner, Tiffany Chi, Seta Degann, Douglas Oberlin, Christoph Buettner
Insulin is a key regulator of adipose tissue lipolysis and impaired adipose tissue insulin action results in unrestrained lipolysis and lipotoxicity, which are hallmarks of the metabolic syndrome and diabetes. Insulin regulates adipose tissue metabolism through direct effects on adipocytes and through signaling in the CNS by dampening sympathetic outflow to the adipose tissue. Here we examined the role of insulin signaling in agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) neurons in regulating both hepatic and adipose tissue insulin action...
April 6, 2017: Diabetes
https://www.readbyqxmd.com/read/28385802/rage-aptamer-blocks-the-development-and-progression-of-experimental-diabetic-nephropathy
#19
Takanori Matsui, Yuichiro Higashimoto, Yuri Nishino, Nobutaka Nakamura, Kei Fukami, Sho-Ichi Yamagishi
Interaction of advanced glycation end products (AGEs) and their receptor (RAGE) plays a central role in diabetic nephropathy. We screened DNA aptamers directed against RAGE (RAGE-aptamers) in vitro, and examined the effects on development and progression of diabetic nephropathy in streptozotocin-induced diabetic rats. RAGE-aptamer bound to RAGE with a dissociation constant of 5.68 nM and resultantly blocked the binding of AGEs to RAGE. When diabetic rats received continuous intraperitoneal injection of RAGE-aptamer from week 7 to 11 of diabetes, the increases in renal NADPH oxidase activity, oxidative stress generation, AGE, RAGE, inflammatory and fibrotic gene and protein levels, macrophage and extracellular matrix accumulation, and albuminuria were significantly suppressed, which were associated with improvement of podocyte damage...
April 6, 2017: Diabetes
https://www.readbyqxmd.com/read/28385801/mechanisms-controlling-glucose-induced-glp-1-secretion-in-human-small-intestine
#20
Emily W Sun, Dayan de Fontgalland, Philippa Rabbitt, Paul Hollington, Luigi Sposato, Steven L Due, David A Wattchow, Christopher K Rayner, Adam M Deane, Richard L Young, Damien J Keating
Intestinal glucose stimulates secretion of the incretin hormone glucagon-like peptide 1 (GLP-1). The mechanisms underlying this pathway have not been fully investigated in humans. In this study, we showed that a 30 minute intraduodenal glucose infusion activated half of all duodenal L cells in humans. This infusion was sufficient to increase plasma GLP-1. With an ex vivo model using human gut tissue specimens, we showed a dose-responsive GLP-1 secretion in ileum at 200mM glucose or above. In ex vivo tissue from duodenum and ileum, but not colon, 300mM glucose potently stimulated GLP-1 release...
April 6, 2017: Diabetes
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