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4481. 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.
4482. 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.
4483. 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.
4484. 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.
4485. 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.
4486. 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.
4487. 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.
4488. 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.
4489. 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.
4490. 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).
4491. 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.
4492. 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.
4493. Plasma C5 glucose-to-2H2O ratio does not provide an accurate assessment of gluconeogenesis during hyperinsulinemic-euglycemic clamps in either nondiabetic or diabetic humans.
作者: Rita Basu.;Visvanathan Chandramouli.;Betty Dicke.;Bernard R Landau.;Robert A Rizza.
来源: Diabetes. 2008年57卷7期1800-4页
Measurement of plasma C2 glucose enrichment is cumbersome. Therefore, the plasma C5 glucose-to-(2)H(2)O rather than the plasma C5-to-C2 glucose ratio commonly has been used to measure gluconeogenesis and glycogenolysis during hyperinsulinemic-euglycemic clamps. The validity of this approach is unknown.
4494. Hormone-sensitive lipase serine phosphorylation and glycerol exchange across skeletal muscle in lean and obese subjects: effect of beta-adrenergic stimulation.
作者: Johan W E Jocken.;Carsten Roepstorff.;Gijs H Goossens.;Paula van der Baan.;Marleen van Baak.;Wim H M Saris.;Bente Kiens.;Ellen E Blaak.
来源: Diabetes. 2008年57卷7期1834-41页
Increased intramuscular triacylglycerol (IMTG) storage is a characteristic of the obese insulin-resistant state. We aimed to investigate whether a blunted fasting or beta-adrenergically mediated lipolysis contributes to this increased IMTG storage in obesity.
4495. Glucose metabolism in vivo in four commonly used inbred mouse strains.
作者: Eric D Berglund.;Candice Y Li.;Greg Poffenberger.;Julio E Ayala.;Patrick T Fueger.;Shannon E Willis.;Marybeth M Jewell.;Alvin C Powers.;David H Wasserman.
来源: Diabetes. 2008年57卷7期1790-9页
To characterize differences in whole-body glucose metabolism between commonly used inbred mouse strains.
4496. Weak proinsulin peptide-major histocompatibility complexes are targeted in autoimmune diabetes in mice.
Weak major histocompatibility complex (MHC) binding of self-peptides has been proposed as a mechanism that may contribute to autoimmunity by allowing for escape of autoreactive T-cells from the thymus. We examined the relationship between the MHC-binding characteristics of a beta-cell antigen epitope and T-cell autoreactivity in a model of autoimmune diabetes.
4497. Serum heat shock protein 27 and diabetes complications in the EURODIAB prospective complications study: a novel circulating marker for diabetic neuropathy.
作者: Gabriella Gruden.;Graziella Bruno.;Nish Chaturvedi.;Davina Burt.;Casper Schalkwijk.;Silvia Pinach.;Coen D Stehouwer.;Daniel R Witte.;John H Fuller.;Paolo Cavallo Perin.; .
来源: Diabetes. 2008年57卷7期1966-70页
Heat shock protein 27 (HSP27) is a member of the small heat shock protein family of proteins. HSP27 expression is enhanced in target tissues of diabetic microvascular complications, and changes in circulating serum HSP27 levels (sHSP27) have been reported in patients with macrovascular disease. We investigated whether sHSP27 levels were associated with micro- and macrovascular complications in type 1 diabetic patients.
4498. Novel de novo mutation in sulfonylurea receptor 1 presenting as hyperinsulinism in infancy followed by overt diabetes in early adolescence.
作者: Maha Abdulhadi-Atwan.;Jeremy Bushman.;Sharona Tornovsky-Babaey.;Avital Perry.;Abdulsalam Abu-Libdeh.;Benjamin Glaser.;Show-Ling Shyng.;David H Zangen.
来源: Diabetes. 2008年57卷7期1935-40页
Congenital hyperinsulinism, usually associated with severe neonatal hypoglycemia, may progress to diabetes, typically during the 4th decade of life in nonpancreatectomized patients. We aimed to genotype the ATP-sensitive K(+) channel in a 10.5-year-old girl presenting with overt diabetes following hyperinsulinism in infancy.
4499. Effect of oral amino acids on counterregulatory responses and cognitive function during insulin-induced hypoglycemia in nondiabetic and type 1 diabetic people.
作者: Paolo Rossetti.;Francesca Porcellati.;Natalia Busciantella Ricci.;Paola Candeloro.;Patrizia Cioli.;K Sreekumaran Nair.;Fausto Santeusanio.;Geremia B Bolli.;Carmine G Fanelli.
来源: Diabetes. 2008年57卷7期1905-17页
Amino acids stimulate glucagon responses to hypoglycemia and may be utilized by the brain. The aim of this study was to assess the responses to hypoglycemia in nondiabetic and type 1 diabetic subjects after ingestion of an amino acid mixture.
4500. Increased GABAergic tone in the ventromedial hypothalamus contributes to suppression of counterregulatory responses after antecedent hypoglycemia.
作者: Owen Chan.;Haiying Cheng.;Raimund Herzog.;Daniel Czyzyk.;Wanling Zhu.;Ajin Wang.;Rory J McCrimmon.;Margretta R Seashore.;Robert S Sherwin.
来源: Diabetes. 2008年57卷5期1363-70页
We have previously demonstrated that modulation of gamma-aminobutyric acid (GABA) inhibitory tone in the ventromedial hypothalamus (VMH), an important glucose-sensing region in the brain, modulates the magnitude of glucagon and sympathoadrenal responses to hypoglycemia. In the current study, we examined whether increased VMH GABAergic tone may contribute to suppression of counterregulatory responses after recurrent hypoglycemia.
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