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Diabetes

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https://www.readbyqxmd.com/read/28515126/radiomanganese-pet-detects-changes-in-functional-%C3%AE-cell-mass-in-mouse-models-of-diabetes
#1
Reinier Hernandez, Stephen A Graves, Trillian Gregg, Halena R VanDeusen, Rachel J Fenske, Haley N Wienkes, Christopher G England, Hector F Valdovinos, Justin J Jeffery, Todd E Barnhart, Gregory W Severin, Robert J Nickles, Michelle E Kimple, Matthew J Merrins, Weibo Cai
The noninvasive measurement of functional β-cell mass would be clinically valuable for monitoring the progression of type 1 and type 2 diabetes, as well as the viability of transplanted insulin-producing cells. Although previous work employing magnetic resonance imaging has shown promise for functional β-cell mass determination through voltage-dependent Ca(2+) channel (VDCC)-mediated internalization of Mn(2+), the clinical utility of this technique is limited by the cytotoxic levels of Mn(2+) contrast agent...
May 17, 2017: Diabetes
https://www.readbyqxmd.com/read/28506962/pair-feeding-but-not-insulin-phloridzin-or-rosiglitazone-treatment-curtails-markers-of-beta-cell-dedifferentiation-in-db-db-mice
#2
Emi Ishida, Ja Young Kim-Muller, Domenico Accili
Beta cell failure is a hallmark of type 2 diabetes. Among several cellular biological mechanisms of cellular dysfunction, we and others have recently proposed that dedifferentiation of beta cells can explain the slowly progressive onset and partial reversibility of beta-cell failure. Accordingly, we provided evidence of such processes in humans and experimental animal models of insulin-resistant diabetes. In this study, we asked whether beta cell dedifferentiation can be prevented with diet or pharmacological treatment of diabetes...
May 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28495880/sox4-allows-facultative-%C3%AE-cell-proliferation-through-repression-of-cdkn1a
#3
Eric E Xu, Shugo Sasaki, Thilo Speckmann, Cuilan Nian, Francis C Lynn
The HMG-box transcription factor, SOX4, is the most highly expressed SOX family protein in pancreatic islets, and mutations in Sox4 are associated with an increased risk of developing type 2 diabetes. We utilized an inducible β-cell knockout mouse model to test the hypothesis that Sox4 is essential for the maintenance of β-cell number during the development of type 2 diabetes. Knockout of Sox4 at 6 weeks of age resulted in time-dependent worsening of glucose tolerance, impairment of insulin secretion, and diabetes by 30 weeks of age...
May 11, 2017: Diabetes
https://www.readbyqxmd.com/read/28490610/mechanisms-of-insulin-resistance-in-primary-and-secondary-non-alcoholic-fatty-liver
#4
Tomas Jelenik, Kirti Kaul, Gilles Séquaris, Ulrich Flögel, Esther Phielix, Jörg Kotzka, Birgit Knebel, Pia Fahlbusch, Tina Hörbelt, Stefan Lehr, Anna Lena Reinbeck, Dirk Müller-Wieland, Irene Esposito, Gerald I Shulman, Julia Szendroedi, Michael Roden
Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance and may result primarily from increased hepatic de novo lipogenesis (PRIM) or secondarily from adipose-tissue lipolysis (SEC). We studied mice with hepatocyte- or adipocyte-specific sterol regulatory-element binding protein-1c (SREBP-1c) overexpression as models of PRIM and SEC. PRIM mice featured increased lipogenic gene expression in liver and adipose tissue. Their selective, liver-specific insulin resistance was associated with increased C18:1-diacylglycerol (DAG) content and protein kinase C (PKC)ε translocation...
May 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28490609/a-genome-wide-association-study-of-ivgtt-based-measures-of-first-phase-insulin-secretion-refines-the-underlying-physiology-of-type-2-diabetes-variants
#5
Andrew R Wood, Anna Jonsson, Anne U Jackson, Nan Wang, Nienke van Leewen, Nicholette D Palmer, Sayuko Kobes, Joris Deelen, Lorena Boquete-Vilarino, Jussi Paananen, Alena Stančáková, Dorret I Boomsma, Eco Jc de Geus, Elisabeth Mw Eekhoff, Andreas Fritsche, Mark Kramer, Giel Nijpels, Annemarie Simonis-Bik, Timon W van Haeften, Anubha Mahajan, Michael Boehnke, Richard N Bergman, Jaakko Tuomilehto, Francis S Collins, Karen L Mohlke, Karina Banasik, Christopher J Groves, Mark I McCarthy, Ewan R Pearson, Andrea Natali, Andrea Mari, Thomas A Buchanan, Kent D Taylor, Anny H Xiang, Anette P Gjesing, Niels Grarup, Hans Eiberg, Oluf Pedersen, Yii-Derr Chen, Markku Laakso, Jill M Norris, Ulf Smith, Lynne E Wagenknecht, Leslie Baier, Donald W Bowden, Torben Hansen, Mark Walker, Richard M Watanabe, Leen M 't Hart, Robert L Hanson, Timothy M Frayling
No abstract text is available yet for this article.
May 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28487437/hypoglycemic-effect-of-combined-ghrelin-and-glucagon-receptor-blockade
#6
Bharath K Mani, Aki Uchida, Young Lee, Sherri Osborne-Lawrence, Maureen J Charron, Roger H Unger, Eric D Berglund, Jeffrey M Zigman
Glucagon receptor (GcgR) blockade has been proposed as an alternative to insulin monotherapy for treating Type 1 diabetes mellitus since deletion or inhibition of GcgRs corrects hyperglycemia in diabetic models. The factors regulating glycemia in a setting devoid of insulin and glucagon function remain unclear, but may include the hormone ghrelin. Not only is ghrelin release controlled by glucose, but also ghrelin has many actions that can raise or reduce falls in blood glucose. Here, we tested the hypothesis that ghrelin rises to minimize hypoglycemia in the absence of glucagon function...
May 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28487436/protective-effect-of-let-7-mirna-family-in-regulating-inflammation-in-diabetes-associated-atherosclerosis
#7
Eoin Brennan, Bo Wang, Aaron McClelland, Muthukumar Mohan, Mariam Marai, Ophelie Beuscart, Sinda Derouiche, Stephen Gray, Raelene Pickering, Chris Tikellis, Monica de Gaetano, Mary Barry, Orina Belton, Syed Tasadaque Ali-Shah, Patrick Guiry, Karin Am Jandeleit-Dahm, Mark E Cooper, Catherine Godson, Phillip Kantharidis
The let-7 miRNA family play a key role in modulating inflammatory responses. Vascular smooth muscle cell (SMC) proliferation, and endothelial cell (EC) dysfunction are critical in the pathogenesis of atherosclerosis, including in the setting of diabetes. Here we report that let-7 levels are decreased in diabetic human carotid plaques and in a model of diabetes-associated atherosclerosis (DAA), the diabetic ApoE(-/-) mouse. In vitro, platelet-derived growth factor (PDGF) and tumor necrosis factor-alpha (TNF-α) induced vascular SMC and EC activation was associated with reduced let-7 miRNA expression, via Lin28b, a negative regulator of let-7 biogenesis...
May 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28483802/glucagon-like-peptide-1-receptor-activation-augments-cardiac-output-and-improves-cardiac-efficiency-in-obese-swine-following-myocardial-infarction
#8
Daniel J Sassoon, Johnathan D Tune, Kieren J Mather, Jillian N Noblet, Mackenzie A Eagleson, Abass M Conteh, Joshua T Sturek, Adam G Goodwill
This study tested the hypothesis that glucagon-like peptide-1 therapies improve cardiac contractile function at rest and in response to adrenergic stimulation in obese swine following myocardial infarction. Obese Ossabaw swine were subjected to gradually developing regional coronary occlusion using an ameroid occluder placed around the left anterior descending coronary artery. Animals received subcutaneous injections of saline or liraglutide (0.005-0.015 mg/kg/day) for 30 days following ameroid placement. Cardiac performance was then assessed at rest and in response to sympathomimetic challenge (dobutamine 0...
May 8, 2017: Diabetes
https://www.readbyqxmd.com/read/28483801/intramyocellular-ceramides-sub-cellular-concentrations-and-fractional-de-novo-synthesis-in-postabsorptive-humans
#9
Jin Ook Chung, Christina Koutsari, Agnieszka U Blachnio-Zabielska, Kazanna C Hames, Michael D Jensen
We investigated the relationship between insulin resistance markers and subsarcolemmal (SS) and intramyofibrillar (IMF) ceramide concentrations, as well as the contribution of plasma palmitate (6.5 h infusion of [U-(13)C]palmitate) to intramyocellular ceramides. Seventy-six postabsorptive men and women had muscle biopsies 1.5 h, 6.5 h and 24 h after starting the tracer infusion. Concentrations and enrichment of muscle ceramides were measured by LC\MS\MS. We found that HOMA-IR, plasma insulin and triglyceride concentrations were positively correlated with SS C16:0 and C18:1 ceramide, but not SS C14:0-Cer, C20:0-Cer, C24:0-Cer, and C24:1-Cer concentrations; IMF ceramide concentrations were not correlated with any metabolic parameters...
May 8, 2017: Diabetes
https://www.readbyqxmd.com/read/28476931/a-genome-wide-association-study-using-a-custom-genotyping-array-identifies-variants-in-gpr158-associated-with-reduced-energy-expenditure-in-american-indians
#10
Paolo Piaggi, Ivica Masindova, Yunhua L Muller, Josep Mercader, Gregory B Wiessner, Peng Chen, Sayuko Kobes, Wen-Chi Hsueh, Milliejoan Mongalo, William C Knowler, Jonathan Krakoff, Robert L Hanson, Clifton Bogardus, Leslie J Baier
Pima Indians living in Arizona suffer from a high prevalence of obesity, and we have previously shown that a relatively lower energy expenditure (EE) predicts weight and fat mass gain in this population. Energy expenditure (EE) is a familial trait (heritability=0.52); therefore, in the current study, we aimed to identify genetic variants that affect EE and thereby influence BMI and body fatness in Pima Indians.Genotypic data from 491,265 variants were analyzed for association with resting metabolic rate (RMR) and 24-h EE assessed in a whole-room calorimeter in 507 and 419 Pima Indians, respectively...
May 5, 2017: Diabetes
https://www.readbyqxmd.com/read/28476930/mitochondrial-targeted-catalase-protects-against-high-fat-diet-induced-muscle-insulin-resistance-by-decreasing-intramuscular-lipid-accumulation
#11
Hui-Young Lee, Jae Sung Lee, Tiago Alves, Warren Ladiges, Peter S Rabinovitch, Michael J Jurczak, Cheol Soo Choi, Gerald I Shulman, Varman T Samuel
We explored the role of reactive oxygen species (ROS) in the pathogenesis of muscle insulin resistance by assessing insulin action in vivo with a hyperinsulinemic-euglycemic clamp in mice expressing a mitochondrially-targeted catalase (MCAT) that were fed regular chow (RC), a high-fat diet (HFD), or undergoing an acute infusion of a lipid emulsion. RC MCAT mice were similar to littermate wild-type (WT) mice. However, HFD MCAT mice were protected from diet-induced insulin resistance. In contrast, an acute lipid infusion caused muscle insulin resistance in both MCAT and WT mice...
May 5, 2017: Diabetes
https://www.readbyqxmd.com/read/28473464/alterations-in-3-hydroxyisobutyrate-and-fgf21-metabolism-are-associated-with-protein-ingestion-induced-insulin-resistance
#12
Lydia-Ann L S Harris, Gordon I Smith, Bruce W Patterson, Raja S Ramaswamy, Adewole Okunade, Shannon C Kelly, Lane C Porter, Samuel Klein, Jun Yoshino, Bettina Mittendorfer
Systemic hyperaminoacidemia, induced by either intravenous amino acid infusion or protein ingestion, reduces insulin-stimulated glucose disposal. Studies in mice suggest that the valine metabolite 3-hydroxyisobutyrate (3-HIB), fibroblast growth factor 21 (FGF21), adiponectin, and non-esterified fatty acids (NEFA) may be involved in the amino acid-mediated insulin resistance. We therefore measured the rate of glucose disposal, and plasma 3-HIB, FGF21, adiponectin, and NEFA concentrations in 30 women during basal conditions and during a hyperinsulinemic-euglycemic clamp procedure (HECP) with and without concomitant ingestion of protein (n=15) or an amount of leucine that matched the amount in the protein (n=15)...
May 4, 2017: Diabetes
https://www.readbyqxmd.com/read/28473463/recessively-inherited-lrba-mutations-cause-autoimmunity-presenting-as-neonatal-diabetes
#13
Matthew B Johnson, Elisa De Franco, Hana Lango-Allen, Aisha Al Senani, Nancy Elbarbary, Zeynep Siklar, Merih Berberoglu, Zineb Imane, Alireza Haghighi, Irfan Ullah, Saif Alyaarubi, Daphne Gardner, Sian Ellard, Andrew T Hattersley, Sarah E Flanagan
Young-onset autoimmune diabetes associated with additional autoimmunity usually reflects a polygenic predisposition but rare cases result from monogenic autoimmunity. Diagnosing monogenic autoimmunity is crucial for patients' prognosis and clinical management. We sought to identify novel genetic causes of autoimmunity presenting with neonatal diabetes (NDM; diagnosis <6 months).We performed exome sequencing in a patient with NDM and autoimmune lymphoproliferative syndrome and his unrelated, unaffected parents and identified compound heterozygous null mutations in LRBA Biallelic LRBA mutations cause Common Variable Immunodeficiency-8, however NDM has not been confirmed in this disorder...
May 4, 2017: Diabetes
https://www.readbyqxmd.com/read/28468960/genetic-disruption-of-adenosine-kinase-in-mouse-pancreatic-%C3%AE-cells-protects-against-high-fat-diet-induced-glucose-intolerance
#14
Guadalupe Navarro, Yassan Abdolazami, Zhengshan Zhao, Haixia Xu, Sooyeon Lee, Neali A Armstrong, Justin P Annes
Islet β-cells adapt to insulin resistance through increased insulin secretion and expansion. Type 2 diabetes (T2D) typically occurs when prolonged insulin resistance exceeds the adaptive capacity of β-cells. Our prior screening efforts led to the discovery that Adenosine kinase (ADK) inhibitors stimulate β-cell replication. Here evaluated whether ADK disruption in mouse β-cells impacts β-cell mass and/or protects against high fat diet (HFD)-induced glucose dysregulation. Mice targeted at the Adk locus were bred to Rip-Cre and Ins1-Cre/ERT(1Lphi) mice to enable constitutive (βADKO) and conditional (iβADKO) disruption of ADK expression in β-cells, respectively...
May 3, 2017: Diabetes
https://www.readbyqxmd.com/read/28468959/dominant-er-stress-inducing-wfs1-mutations-underlie-a-genetic-syndrome-of-neonatal-infancy-onset-diabetes-congenital-sensorineural-deafness-and-congenital-cataracts
#15
Elisa De Franco, Sarah E Flanagan, Takuya Yagi, Damien Abreu, Jana Mahadevan, Matthew B Johnson, Garan Jones, Fernanda Acosta, Mphele Mulaudzi, Ngee Lek, Vera Oh, Oliver Petz, Richard Caswell, Sian Ellard, Fumihiko Urano, Andrew T Hattersley
Neonatal diabetes is frequently part of a complex syndrome with extra-pancreatic features: 18 genes causing syndromic neonatal diabetes have been identified to date. There remain patients with neonatal diabetes who have novel genetic syndromes.We performed exome sequencing in a patient and his unrelated, unaffected parents to identify the genetic aetiology of a syndrome characterized by neonatal diabetes, sensorineural deafness and congenital cataracts. Further testing was performed in 311 patients with diabetes diagnosed before 1 year of age in whom all known genetic causes had been excluded...
May 3, 2017: Diabetes
https://www.readbyqxmd.com/read/28465407/role-of-nrf2-signaling-in-the-regulation-of-vascular-bk-channel-beta-1-subunit-expression-and-bk-channel-function-in-high-fat-diet-induced-diabetic-mice
#16
Tong Lu, Xiaojing Sun, Yong Li, Qiang Chai, Xiao-Li Wang, Hon-Chi Lee
The large conductance Ca(2+)-activated K(+) (BK) channel β1 subunit (BK-β1) is a key modulator of BK channel electrophysiology and the downregulation of BK-β1 protein expression in vascular smooth muscle cells (SMCs) underlies diabetic vascular dysfunction. In this study, we hypothesized that the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway plays a significant role in the regulation of coronary BK channel function and vasodilation in high fat diet (HFD)-induced obese/diabetic mice...
May 2, 2017: Diabetes
https://www.readbyqxmd.com/read/28461456/elovl6-deficiency-improves-glycemic-control-in-diabetic-db-db-mice-by-expanding-%C3%AE-cell-mass-and-increasing-insulin-secretory-capacity
#17
Hui Zhao, Takashi Matsuzaka, Yuta Nakano, Kaori Motomura, Nie Tang, Tomotaka Yokoo, Yuka Okajima, Song-Iee Han, Yoshinori Takeuchi, Yuichi Aita, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Motohiro Sekiya, Naoya Yahagi, Yoshimi Nakagawa, Hirohito Sone, Nobuhiro Yamada, Hitoshi Shimano
Dysfunctional fatty acid (FA) metabolism plays an important role in the pathogenesis of β-cell dysfunction and loss of β-cell mass in type 2 diabetes (T2D). Elovl6 is a microsomal enzyme that is responsible for converting C16 saturated and monounsaturated FAs into C18 species. We previously showed that Elovl6 played a critical role in the development of obesity-induced insulin resistance by modifying FA composition. To further define its role in T2D development, we assessed the effects of Elovl6 deletion in leptin receptor-deficient C57BL/KsJ db/db mice, a model of T2D...
May 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28450418/statement-of-retraction-egfr-tyrosine-kinase-inhibitor-pd153035-improves-glucose-tolerance-and-insulin-action-in-high-fat-diet-fed-mice-diabetes-2009-58-2910-2919-doi-10-2337-db08-0506-pmid-19696185
#18
Patricia O Prada, Eduardo R Ropelle, Rosa H Mourão, Claudio T de Souza, Jose R Pauli, Dennys E Cintra, André Schenka, Silvana A Rocco, Roberto Rittner, Kleber G Franchini, José Vassallo, Lício A Velloso, José B Carvalheira, Mario J A Saad
No abstract text is available yet for this article.
April 27, 2017: Diabetes
https://www.readbyqxmd.com/read/28450417/gdf11-attenuates-development-of-type-2-diabetes-via-improvement-of-islet-%C3%AE-cell-function-and-survival
#19
Huan Li, Yixiang Li, Lingwei Xiang, JiaJia Zhang, Biao Zhu, Lin Xiang, Jing Dong, Min Liu, Guangda Xiang
Growth differentiation factor 11 (GDF11) has been implicated in the regulation of islet development and a variety of aging conditions, but little is known about the physiological functions of GDF11 in adult pancreatic islets. Here, we showed that systematic replenishment of GDF11 not only preserved insulin secretion but also improved the survival and morphology of β cells as well as improved glucose metabolism in both non-genetic and genetic mouse models of type 2 diabetes (T2D). Conversely, anti-GDF11 monoclonal antibody treatment caused β cell failure and lethal T2D...
April 27, 2017: Diabetes
https://www.readbyqxmd.com/read/28446519/cationic-polystyrene-resolves-nonalcoholic-steatohepatitis-nash-obesity-and-metabolic-disorders-by-promoting-eubiosis-of-gut-microbiota-and-decreasing-endotoxemia
#20
Airu Zhu, Jingjing Chen, Pengfei Wu, Mei Luo, Yilan Zeng, Han Zheng, Li Zhang, Zishou Cheng, Qun Sun, Wenwen Li, Yixiang Duan, Danmei Su, Zhixiong Xiao, Zhongping Duan, Sujun Zheng, Li Bei, Xiaohui Zhang, Zhongyuan Ju, Richard Hu, Stephen J Pandol, Yuan-Ping Han
A pandemic of metabolic diseases, consisting of type-2 diabetes, non-alcoholic fatty liver diseases (NAFLD) and obesity, has imposed critical challenges for societies worldwide, prompting investigation of underlying mechanisms and exploration of low cost and effective treatment. In this report, we demonstrate that metabolic disorders in mice generated by feeding with a high-fat diet without dietary vitamin D (HD) can be prevented by oral administration of polycationic amine resin. Oral administration of cholestyramine , but not the control uncharged polystyrene, was able to sequester negatively charged bacterial endotoxin in the gut, leading to (1) reducing plasma endotoxin levels, (2) resolving systemic inflammation and hepatic steatohepatitis,and (3) improving insulin sensitivity...
April 26, 2017: Diabetes
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