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4341. Amplified hormonal counterregulatory responses to hypoglycemia in rats after systemic delivery of a SUR-1-selective K(+) channel opener?
作者: Xiaoning Fan.;Yuyan Ding.;Haiying Cheng.;Dorte X Gram.;Robert S Sherwin.;Rory J McCrimmon.
来源: Diabetes. 2008年57卷12期3327-34页
In glucose-sensing neurons, ATP-sensitive K(+) channels (K(ATP) channels) are thought to translate metabolic signals into an alteration in neuronal firing rates. Because these neurons express the Kir6.2/SUR-1 isoform of the K(ATP) channel, we sought to examine the therapeutic potential of the SUR-1-selective potassium channel opener (KCO), NN414, to amplify counterregulatory response to hypoglycemia.
4342. Exclusion of polymorphisms in carnosinase genes (CNDP1 and CNDP2) as a cause of diabetic nephropathy in type 1 diabetes: results of large case-control and follow-up studies.
作者: Krzysztof Wanic.;Grzegorz Placha.;Jonathon Dunn.;Adam Smiles.;James H Warram.;Andrzej S Krolewski.
来源: Diabetes. 2008年57卷9期2547-51页
Recently, an association was found between diabetic nephropathy and the D18S880 microsatellite, located in the carnosinase gene (CNDP1) on chromosome 18q. Alleles of this microsatellite encode for a variable number of leucine residues (from four to seven) in the leader peptide of the carnosinase precursor. The frequency of subjects homozygous for the five leucines was higher in control subjects than in case subjects in studies focusing on type 2 diabetic patients. To test whether this finding can be extended to type 1 diabetic patients, we carried out a comprehensive study on association between diabetic nephropathy and the D18S880 microsatellite and 21 additional SNPs that tagged the genomic region containing CNDP1 and CNDP2.
4345. Ablation of AMP-activated protein kinase alpha2 activity exacerbates insulin resistance induced by high-fat feeding of mice.
作者: Nobuharu Fujii.;Richard C Ho.;Yasuko Manabe.;Niels Jessen.;Taro Toyoda.;William L Holland.;Scott A Summers.;Michael F Hirshman.;Laurie J Goodyear.
来源: Diabetes. 2008年57卷11期2958-66页
We determined whether muscle AMP-activated protein kinase (AMPK) has a role in the development of insulin resistance.
4346. Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats.
作者: Taiga Shibata.;Keiko Naruse.;Hideki Kamiya.;Mika Kozakae.;Masaki Kondo.;Yutaka Yasuda.;Nobuhisa Nakamura.;Kimiko Ota.;Takahiro Tosaki.;Takashi Matsuki.;Eitaro Nakashima.;Yoji Hamada.;Yutaka Oiso.;Jiro Nakamura.
来源: Diabetes. 2008年57卷11期3099-107页
Mesenchymal stem cells (MSCs) have been reported to secrete various cytokines that exhibit angiogenic and neurosupportive effects. This study was conducted to investigate the effects of MSC transplantation on diabetic polyneuropathy (DPN) in rats.
4347. Forkhead transcription factors (FoxOs) promote apoptosis of insulin-resistant macrophages during cholesterol-induced endoplasmic reticulum stress.
作者: Takafumi Senokuchi.;Chien-Ping Liang.;Tracie A Seimon.;Seongah Han.;Michihiro Matsumoto.;Alexander S Banks.;Ji-Hye Paik.;Ronald A DePinho.;Domenico Accili.;Ira Tabas.;Alan R Tall.
来源: Diabetes. 2008年57卷11期2967-76页
Endoplasmic reticulum stress increases macrophage apoptosis, contributing to the complications of atherosclerosis. Insulin-resistant macrophages are more susceptible to endoplasmic reticulum stress-associated apoptosis probably contributing to macrophage death and necrotic core formation in atherosclerotic plaques in type 2 diabetes. However, the molecular mechanisms of increased apoptosis in insulin-resistant macrophages remain unclear.
4348. Population-specific risk of type 2 diabetes conferred by HNF4A P2 promoter variants: a lesson for replication studies.
作者: Inês Barroso.;Jian'an Luan.;Eleanor Wheeler.;Pamela Whittaker.;Jon Wasson.;Eleftheria Zeggini.;Michael N Weedon.;Sarah Hunt.;Ranganath Venkatesh.;Timothy M Frayling.;Marcos Delgado.;Rosalind J Neuman.;Jinghua Zhao.;Richard Sherva.;Benjamin Glaser.;Mark Walker.;Graham Hitman.;Mark I McCarthy.;Andrew T Hattersley.;M Alan Permutt.;Nicholas J Wareham.;Panagiotis Deloukas.
来源: Diabetes. 2008年57卷11期3161-5页
Single nucleotide polymorphisms (SNPs) in the P2 promoter region of HNF4A were originally shown to be associated with predisposition for type 2 diabetes in Finnish, Ashkenazi, and, more recently, Scandinavian populations, but they generated conflicting results in additional populations. We aimed to investigate whether data from a large-scale mapping approach would replicate this association in novel Ashkenazi samples and in U.K. populations and whether these data would allow us to refine the association signal.
4349. Decreased cardiac glutathione peroxidase levels and enhanced mandibular apoptosis in malformed embryos of diabetic rats.
To characterize normal and malformed embryos within the same litters from control and diabetic rats for expression of genes related to metabolism of reactive oxygen species (ROS) or glucose as well as developmental genes.
4350. Beta-cell proliferation, but not neogenesis, following 60% partial pancreatectomy is impaired in the absence of FoxM1.
This study was designed to determine whether the transcription factor FoxM1 was required for regeneration of beta-cell mass via proliferation and/or neogenesis in the adult after 60% partial pancreatectomy (PPx).
4351. Peripheral, but not central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats.
作者: Ruben Nogueiras.;Christelle Veyrat-Durebex.;Paula M Suchanek.;Marcella Klein.;Johannes Tschöp.;Charles Caldwell.;Stephen C Woods.;Gabor Wittmann.;Masahiko Watanabe.;Zsolt Liposits.;Csaba Fekete.;Ofer Reizes.;Francoise Rohner-Jeanrenaud.;Matthias H Tschöp.
来源: Diabetes. 2008年57卷11期2977-91页
Blockade of the CB1 receptor is one of the promising strategies for the treatment of obesity. Although antagonists suppress food intake and reduce body weight, the role of central versus peripheral CB1 activation on weight loss and related metabolic parameters remains to be elucidated. We therefore specifically assessed and compared the respective potential relevance of central nervous system (CNS) versus peripheral CB1 receptors in the regulation of energy homeostasis and lipid and glucose metabolism in diet-induced obese (DIO) rats.
4352. Endurance exercise as a countermeasure for aging.
作者: Ian R Lanza.;Daniel K Short.;Kevin R Short.;Sreekumar Raghavakaimal.;Rita Basu.;Michael J Joyner.;Joseph P McConnell.;K Sreekumaran Nair.
来源: Diabetes. 2008年57卷11期2933-42页
We determined whether reduced insulin sensitivity, mitochondrial dysfunction, and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity.
4353. Predicting type 2 diabetes based on polymorphisms from genome-wide association studies: a population-based study.
作者: Mandy van Hoek.;Abbas Dehghan.;Jacqueline C M Witteman.;Cornelia M van Duijn.;André G Uitterlinden.;Ben A Oostra.;Albert Hofman.;Eric J G Sijbrands.;A Cecile J W Janssens.
来源: Diabetes. 2008年57卷11期3122-8页
Prediction of type 2 diabetes based on genetic testing might improve identification of high-risk subjects. Genome-wide association (GWA) studies identified multiple new genetic variants that associate with type 2 diabetes. The predictive value of genetic testing for prediction of type 2 diabetes in the general population is unclear.
4354. Small interfering RNA-mediated suppression of proislet amyloid polypeptide expression inhibits islet amyloid formation and enhances survival of human islets in culture.
作者: Lucy Marzban.;Alejandra Tomas.;Thomas C Becker.;Lawrence Rosenberg.;Jose Oberholzer.;Paul E Fraser.;Philippe A Halban.;C Bruce Verchere.
来源: Diabetes. 2008年57卷11期3045-55页
Islet amyloid, formed by aggregation of the beta-cell peptide islet amyloid polypeptide (IAPP; amylin), is a pathological characteristic of pancreatic islets in type 2 diabetes. Toxic IAPP aggregates likely contribute to the progressive loss of beta-cells in this disease. We used cultured human islets as an ex vivo model of amyloid formation to investigate whether suppression of proIAPP expression would inhibit islet amyloid formation and enhance beta-cell survival and function.
4355. Two single nucleotide polymorphisms identify the highest-risk diabetes HLA genotype: potential for rapid screening.
作者: Jennifer M Barker.;Taylor M Triolo.;Theresa A Aly.;Erin E Baschal.;Sunanda R Babu.;Adam Kretowski.;Marian J Rewers.;George S Eisenbarth.
来源: Diabetes. 2008年57卷11期3152-5页
People with the HLA genotype DRB1*0301-DQA1*0501-DQB1*0201/DRB1*04-DQA1*0301-DQB1*0302 (DR3/4-DQ8) are at the highest risk of developing type 1 diabetes. We sought to find an inexpensive, rapid test to identify DR3/4-DQ8 subjects using two single nucleotide polymorphisms (SNPs).
4356. Diffusion tensor imaging identifies deficits in white matter microstructure in subjects with type 1 diabetes that correlate with reduced neurocognitive function.
作者: Christopher T Kodl.;Daniel T Franc.;Jyothi P Rao.;Fiona S Anderson.;William Thomas.;Bryon A Mueller.;Kelvin O Lim.;Elizabeth R Seaquist.
来源: Diabetes. 2008年57卷11期3083-9页
Long-standing type 1 diabetes is associated with deficits on neurocognitive testing that suggest central white matter dysfunction. This study investigated whether diffusion tensor imaging (DTI), a type of magnetic resonance imaging that measures white matter integrity quantitatively, could identify white matter microstructural deficits in patients with long-standing type 1 diabetes and whether these differences would be associated with deficits found by neurocognitive tests.
4357. Targeting CD22 reprograms B-cells and reverses autoimmune diabetes.
作者: Paolo Fiorina.;Andrea Vergani.;Shirine Dada.;Mollie Jurewicz.;Masie Wong.;Kenneth Law.;Erxi Wu.;Ze Tian.;Reza Abdi.;Indira Guleria.;Scott Rodig.;Kyri Dunussi-Joannopoulos.;Jeffrey Bluestone.;Mohamed H Sayegh.
来源: Diabetes. 2008年57卷11期3013-24页
To investigate a B-cell-depleting strategy to reverse diabetes in naïve NOD mice.
4358. Transforming growth factor-beta suppresses the activation of CD8+ T-cells when naive but promotes their survival and function once antigen experienced: a two-faced impact on autoimmunity.
作者: Christophe M Filippi.;Amy E Juedes.;Janine E Oldham.;Ellie Ling.;Lisa Togher.;Yufeng Peng.;Richard A Flavell.;Matthias G von Herrath.
来源: Diabetes. 2008年57卷10期2684-92页
Transforming growth factor-beta (TGF-beta) can exhibit strong immune suppression but has also been shown to promote T-cell growth. We investigated the differential effect of this cytokine on CD8(+) T-cells in autoimmunity and antiviral immunity.
4359. Comprehensive association study of type 2 diabetes and related quantitative traits with 222 candidate genes.
作者: Kyle J Gaulton.;Cristen J Willer.;Yun Li.;Laura J Scott.;Karen N Conneely.;Anne U Jackson.;William L Duren.;Peter S Chines.;Narisu Narisu.;Lori L Bonnycastle.;Jingchun Luo.;Maurine Tong.;Andrew G Sprau.;Elizabeth W Pugh.;Kimberly F Doheny.;Timo T Valle.;Gonçalo R Abecasis.;Jaakko Tuomilehto.;Richard N Bergman.;Francis S Collins.;Michael Boehnke.;Karen L Mohlke.
来源: Diabetes. 2008年57卷11期3136-44页
Type 2 diabetes is a common complex disorder with environmental and genetic components. We used a candidate gene-based approach to identify single nucleotide polymorphism (SNP) variants in 222 candidate genes that influence susceptibility to type 2 diabetes.
4360. Type 1 diabetic akita mouse hearts are insulin sensitive but manifest structurally abnormal mitochondria that remain coupled despite increased uncoupling protein 3.
作者: Heiko Bugger.;Sihem Boudina.;Xiao Xuan Hu.;Joseph Tuinei.;Vlad G Zaha.;Heather A Theobald.;Ui Jeong Yun.;Alfred P McQueen.;Benjamin Wayment.;Sheldon E Litwin.;E Dale Abel.
来源: Diabetes. 2008年57卷11期2924-32页
Fatty acid-induced mitochondrial uncoupling and oxidative stress have been proposed to reduce cardiac efficiency and contribute to cardiac dysfunction in type 2 diabetes. We hypothesized that mitochondrial uncoupling may also contribute to reduced cardiac efficiency and contractile dysfunction in the type 1 diabetic Akita mouse model (Akita).
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