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4541. Association analysis in african americans of European-derived type 2 diabetes single nucleotide polymorphisms from whole-genome association studies.
作者: Joshua P Lewis.;Nicholette D Palmer.;Pamela J Hicks.;Michele M Sale.;Carl D Langefeld.;Barry I Freedman.;Jasmin Divers.;Donald W Bowden.
来源: Diabetes. 2008年57卷8期2220-5页
Several whole-genome association studies have reported identification of type 2 diabetes susceptibility genes in various European-derived study populations. Little investigation of these loci has been reported in other ethnic groups, specifically African Americans. Striking differences exist between these populations, suggesting they may not share identical genetic risk factors. Our objective was to examine the influence of type 2 diabetes genes identified in whole-genome association studies in a large African American case-control population.
4542. Protein kinase C-delta mediates neuronal apoptosis in the retinas of diabetic rats via the Akt signaling pathway.
作者: Young-Hee Kim.;Yoon-Sook Kim.;Chang-Hwan Park.;In-Yong Chung.;Ji-Myong Yoo.;Jae-Geun Kim.;Byung-Ju Lee.;Sang-Soo Kang.;Gyeong-Jae Cho.;Wan-Sung Choi.
来源: Diabetes. 2008年57卷8期2181-90页
Protein kinase C (PKC)-delta, an upstream regulator of the Akt survival pathway, contributes to cellular dysfunction in the pathogenesis of diabetes. Herein, we examined the role of PKC-delta in neuronal apoptosis through Akt in the retinas of diabetic rats.
4543. Heritability of proliferative diabetic retinopathy.
作者: Kustaa Hietala.;Carol Forsblom.;Paula Summanen.;Per-Henrik Groop.; .
来源: Diabetes. 2008年57卷8期2176-80页
Diabetic nephropathy clusters in families, suggesting that genetic factors play a role in its pathogenesis. We investigated whether similar clustering exists for proliferative retinopathy in families with two or more siblings with type 1 diabetes.
4544. Autocrine IGF-1 action in adipocytes controls systemic IGF-1 concentrations and growth.
作者: Nora Klöting.;Linda Koch.;Thomas Wunderlich.;Matthias Kern.;Karen Ruschke.;Wilhelm Krone.;Jens C Brüning.;Matthias Blüher.
来源: Diabetes. 2008年57卷8期2074-82页
IGF-1 and the IGF-1 receptor (IGF-1R) have been implicated in the regulation of adipocyte differentiation and lipid accumulation in vitro.
4545. Activation of peroxisome proliferator-activated receptor beta/delta inhibits lipopolysaccharide-induced cytokine production in adipocytes by lowering nuclear factor-kappaB activity via extracellular signal-related kinase 1/2.
作者: Ricardo Rodríguez-Calvo.;Lucía Serrano.;Teresa Coll.;Norman Moullan.;Rosa M Sánchez.;Manuel Merlos.;Xavier Palomer.;Juan C Laguna.;Liliane Michalik.;Walter Wahli.;Manuel Vázquez-Carrera.
来源: Diabetes. 2008年57卷8期2149-57页
Chronic activation of the nuclear factor-kappaB (NF-kappaB) in white adipose tissue leads to increased production of pro-inflammatory cytokines, which are involved in the development of insulin resistance. It is presently unknown whether peroxisome proliferator-activated receptor (PPAR) beta/delta activation prevents inflammation in adipocytes.
4546. Evaluation of the association of IGF2BP2 variants with type 2 diabetes in French Caucasians.
作者: Konsta Duesing.;Ghazaleh Fatemifar.;Guillaume Charpentier.;Michel Marre.;Jean Tichet.;Serge Hercberg.;Beverley Balkau.;Philippe Froguel.;Fernando Gibson.
来源: Diabetes. 2008年57卷7期1992-6页
We performed a comprehensive genetic association study of common variation spanning the IGF2BP2 locus in order to replicate the association of the "confirmed" type 2 diabetes susceptibility variants rs4402960 and rs1470579 in the French Caucasian population and to further characterize the susceptibility variants at this novel locus.
4547. Association of FTO with obesity-related traits in the Cebu Longitudinal Health and Nutrition Survey (CLHNS) Cohort.
作者: Amanda F Marvelle.;Leslie A Lange.;Li Qin.;Linda S Adair.;Karen L Mohlke.
来源: Diabetes. 2008年57卷7期1987-91页
The underlying genetic component of obesity-related traits is not well understood, and there is limited evidence to support genetic association shared across multiple studies, populations, and environmental contexts. The present study investigated the association between candidate variants and obesity-related traits in a sample of 1,886 adult Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) cohort.
4548. Activation of estrogen receptor is crucial for resveratrol-stimulating muscular glucose uptake via both insulin-dependent and -independent pathways.
作者: Jen-Ying Deng.;Po-Shiuan Hsieh.;Jiung-Pang Huang.;Long-Sheng Lu.;Li-Man Hung.
来源: Diabetes. 2008年57卷7期1814-23页
Estradiol (E(2)) is known to modulate insulin sensitivity and, consequently, glucose homeostasis. Resveratrol (RSV), an agonist of estrogen receptor (ER), has exerted antihyperglycemic effects in streptozotocin-induced type 1 diabetic rats in our previous study and was also shown to improve insulin resistance in other reports. However, it remains unknown whether activation of ER is involved in the metabolic effects of RSV via insulin-dependent and -independent mechanisms.
4549. Blockade of alpha4 integrin signaling ameliorates the metabolic consequences of high-fat diet-induced obesity.
作者: Chloé C Féral.;Jaap G Neels.;Christiane Kummer.;Marina Slepak.;Jerrold M Olefsky.;Mark H Ginsberg.
来源: Diabetes. 2008年57卷7期1842-51页
Many prevalent diseases of advanced societies, such as obesity-induced type 2 diabetes, are linked to indolent mononuclear cell-dependent inflammation. We previously proposed that blockade of alpha4 integrin signaling can inhibit inflammation while limiting mechanism-based toxicities of loss of alpha4 function. Thus, we hypothesized that mice bearing an alpha4(Y991A) mutation, which blocks signaling, would be protected from development of high-fat diet-induced insulin resistance.
4550. Circulating retinol-binding protein-4 concentration might reflect insulin resistance-associated iron overload.
The mechanisms behind the association between retinol-binding protein-4 (RBP4) and insulin resistance are not well understood. An interaction between iron and vitamin A status, of which RBP4 is a surrogate, has long been recognized. We hypothesized that iron-associated insulin resistance could be behind the impaired insulin action caused by RBP4.
4551. Haplotype structure of the ENPP1 Gene and Nominal Association of the K121Q missense single nucleotide polymorphism with glycemic traits in the Framingham Heart Study.
作者: Elliot S Stolerman.;Alisa K Manning.;Jarred B McAteer.;Josée Dupuis.;Caroline S Fox.;L Adrienne Cupples.;James B Meigs.;Jose C Florez.
来源: Diabetes. 2008年57卷7期1971-7页
A recent meta-analysis demonstrated a nominal association of the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) K-->Q missense single nucleotide polymorphism (SNP) at position 121 with type 2 diabetes. We set out to confirm the association of ENPP1 K121Q with hyperglycemia, expand this association to insulin resistance traits, and determine whether the association stems from K121Q or another variant in linkage disequilibrium with it.
4552. Association analysis of type 2 diabetes Loci in type 1 diabetes.
作者: Hui-Qi Qu.;Struan F A Grant.;Jonathan P Bradfield.;Cecilia Kim.;Edward Frackelton.;Hakon Hakonarson.;Constantin Polychronakos.
来源: Diabetes. 2008年57卷7期1983-6页
To search for a possible association of type 1 diabetes with 10 validated type 2 diabetes loci, i.e., PPARG, KCNJ11, WFS1, HNF1B, IDE/HHEX, SLC30A8, CDKAL1, CDKN2A/B, IGF2BP2, and FTO/RPGRIP1L.
4553. Protein engineering strategies for sustained glucagon-like peptide-1 receptor-dependent control of glucose homeostasis.
作者: Kristen M Picha.;Mark R Cunningham.;Daniel J Drucker.;Ashok Mathur.;Tatiana Ort.;Michael Scully.;Avery Soderman.;Tracy Spinka-Doms.;Vedrana Stojanovic-Susulic.;Beth Ann Thomas.;Karyn T O'Neil.
来源: Diabetes. 2008年57卷7期1926-34页
We have developed a novel platform for display and delivery of bioactive peptides that links the biological properties of the peptide to the pharmacokinetic properties of an antibody. Peptides engineered in the MIMETIBODY platform have improved biochemical and biophysical properties that are quite distinct from those of Fc-fusion proteins. CNTO736 is a glucagon-like peptide 1 (GLP-1) receptor agonist engineered in our MIMETIBODY platform. It retains many activities of native GLP-1 yet has a significantly enhanced pharmacokinetic profile. Our goal was to develop a long-acting GLP-1 receptor agonist with sustained efficacy.
4554. RAGE and modulation of ischemic injury in the diabetic myocardium.
作者: Loredana G Bucciarelli.;Radha Ananthakrishnan.;Yuying C Hwang.;Michiyo Kaneko.;Fei Song.;David R Sell.;Christopher Strauch.;Vincent M Monnier.;Shi Fang Yan.;Ann Marie Schmidt.;Ravichandran Ramasamy.
来源: Diabetes. 2008年57卷7期1941-51页
Subjects with diabetes experience an increased risk of myocardial infarction and cardiac failure compared with nondiabetic age-matched individuals. The receptor for advanced glycation end products (RAGE) is upregulated in diabetic tissues. In this study, we tested the hypothesis that RAGE affected ischemia/reperfusion (I/R) injury in the diabetic myocardium. In diabetic rat hearts, expression of RAGE and its ligands was enhanced and localized particularly to both endothelial cells and mononuclear phagocytes.
4555. Improved vascular engraftment and graft function after inhibition of the angiostatic factor thrombospondin-1 in mouse pancreatic islets.
作者: Johan Olerud.;Magnus Johansson.;Jack Lawler.;Nils Welsh.;Per-Ola Carlsson.
来源: Diabetes. 2008年57卷7期1870-7页
Insufficient development of a new intra-islet capillary network after transplantation may be one contributing factor to the failure of islet grafts in clinical transplantation. The present study tested the hypothesis that the angiostatic factor thrombospondin-1 (TSP-1), which is normally present in islets, restricts intra-islet vascular expansion posttransplantation.
4556. Protective role of programmed death 1 ligand 1 (PD-L1)in nonobese diabetic mice: the paradox in transgenic models.
作者: Chia-Jen Wang.;Feng-Cheng Chou.;Chi-Hong Chu.;Jen-Chine Wu.;Shih-Hua Lin.;Deh-Ming Chang.;Huey-Kang Sytwu.
来源: Diabetes. 2008年57卷7期1861-9页
Coinhibitory signals mediated via programmed death 1 (PD-1) receptor play a critical role in downregulating immune responses and in maintaining peripheral tolerance. Programmed death 1 ligand 1 (PD-L1), the interacting ligand for PD-1, widely expressed in many cell types, acts as a tissue-specific negative regulator of pathogenic T-cell responses. We investigated the protective potential of PD-L1 on autoimmune diabetes by transgenically overexpressing PD-L1 in pancreatic beta-cells in nonobese diabetic (NOD) mice.
4557. Human adenovirus type 36 enhances glucose uptake in diabetic and nondiabetic human skeletal muscle cells independent of insulin signaling.
作者: Zhong Q Wang.;William T Cefalu.;Xian H Zhang.;Yongmei Yu.;Jianhua Qin.;Leslie Son.;Pamela M Rogers.;Nazar Mashtalir.;Justin R Bordelon.;Jianping Ye.;Nikhil V Dhurandhar.
来源: Diabetes. 2008年57卷7期1805-13页
Human adenovirus type 36 (Ad-36) increases adiposity but improves insulin sensitivity in experimentally infected animals. We determined the ability of Ad-36 to increase glucose uptake by human primary skeletal muscle (HSKM) cells.
4558. Hyperglycemia-induced reactive oxygen species toxicity to endothelial cells is dependent on paracrine mediators.
This study determined the effects of high glucose exposure and cytokine treatment on generation of reactive oxygen species (ROS) and activation of inflammatory and apoptotic pathways in human retinal endothelial cells (HRECs).
4559. MAPK kinase kinase-1 is essential for cytokine-induced c-Jun NH2-terminal kinase and nuclear factor-kappaB activation in human pancreatic islet cells.
The transcription factor nuclear factor-kappaB (NF-kappaB) and the mitogen-activated protein kinases (MAPKs) c-Jun NH(2)-terminal kinase (JNK) 1/2 are known to play decisive roles in cytokine-induced damage of rodent beta-cells. The upstream events by which these factors are activated in response to cytokines are, however, uncharacterized. The aim of the present investigation was to elucidate a putative role of the MAPK kinase kinase-1 (MEKK-1) in cytokine-induced signaling.
4560. Immunoglobulin-like transcript 3-Fc suppresses T-cell responses to allogeneic human islet transplants in hu-NOD/SCID mice.
作者: George Vlad.;Vivette D D'Agati.;Qing-Yin Zhang.;Zhuoru Liu.;Eric K Ho.;Thalachallour Mohanakumar.;Mark A Hardy.;Raffaello Cortesini.;Nicole Suciu-Foca.
来源: Diabetes. 2008年57卷7期1878-86页
The aim of our study was to explore the immunomodulatory activity of soluble immunoglobulin (Ig)-like transcript (ILT) 3-Fc in pancreatic islet transplantation and to determine its mechanism of action.
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