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4261. Intracerebroventricular administration of neuropeptide Y induces hepatic insulin resistance via sympathetic innervation.
作者: Anita M van den Hoek.;Caroline van Heijningen.;Janny P Schröder-van der Elst.;D Margriet Ouwens.;Louis M Havekes.;Johannes A Romijn.;Andries Kalsbeek.;Hanno Pijl.
来源: Diabetes. 2008年57卷9期2304-10页
We recently showed that intracerebroventricular infusion of neuropeptide Y (NPY) hampers inhibition of endogenous glucose production (EGP) by insulin in mice. The downstream mechanisms responsible for these effects of NPY remain to be elucidated. Therefore, the aim of this study was to establish whether intracerebroventricular NPY administration modulates the suppressive action of insulin on EGP via hepatic sympathetic or parasympathetic innervation.
4262. Extension of type 2 diabetes genome-wide association scan results in the diabetes prevention program.
作者: Allan F Moore.;Kathleen A Jablonski.;Jarred B McAteer.;Richa Saxena.;Toni I Pollin.;Paul W Franks.;Robert L Hanson.;Alan R Shuldiner.;William C Knowler.;David Altshuler.;Jose C Florez.; .
来源: Diabetes. 2008年57卷9期2503-10页
Genome-wide association scans (GWASs) have identified novel diabetes-associated genes. We evaluated how these variants impact diabetes incidence, quantitative glycemic traits, and response to preventive interventions in 3,548 subjects at high risk of type 2 diabetes enrolled in the Diabetes Prevention Program (DPP), which examined the effects of lifestyle intervention, metformin, and troglitazone versus placebo.
4263. Metabolic phenotypes, vascular complications, and premature deaths in a population of 4,197 patients with type 1 diabetes.
作者: Ville-Petteri Mäkinen.;Carol Forsblom.;Lena M Thorn.;Johan Wadén.;Daniel Gordin.;Outi Heikkilä.;Kustaa Hietala.;Laura Kyllönen.;Janne Kytö.;Milla Rosengård-Bärlund.;Markku Saraheimo.;Nina Tolonen.;Maija Parkkonen.;Kimmo Kaski.;Mika Ala-Korpela.;Per-Henrik Groop.; .
来源: Diabetes. 2008年57卷9期2480-7页
Poor glycemic control, elevated triglycerides, and albuminuria are associated with vascular complications in diabetes. However, few studies have investigated combined associations between metabolic markers, diabetic kidney disease, retinopathy, hypertension, obesity, and mortality. Here, the goal was to reveal previously undetected association patterns between clinical diagnoses and biochemistry in the FinnDiane dataset.
4264. Carcinoembryonic antigen-related cell adhesion molecule 1: a link between insulin and lipid metabolism.
作者: Anthony M DeAngelis.;Garrett Heinrich.;Tong Dai.;Thomas A Bowman.;Payal R Patel.;Sang Jun Lee.;Eun-Gyoung Hong.;Dae Young Jung.;Anke Assmann.;Rohit N Kulkarni.;Jason K Kim.;Sonia M Najjar.
来源: Diabetes. 2008年57卷9期2296-303页
Liver-specific inactivation of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) by a dominant-negative transgene (l-SACC1 mice) impaired insulin clearance, caused insulin resistance, and increased hepatic lipogenesis. To discern whether this phenotype reflects a physiological function of CEACAM1 rather than the effect of the dominant-negative transgene, we characterized the metabolic phenotype of mice with null mutation of the Ceacam1 gene (Cc1(-/-)).
4265. Pioglitazone decreases fasting and postprandial endogenous glucose production in proportion to decrease in hepatic triglyceride content.
作者: Balasubramanian Ravikumar.;Jean Gerrard.;Chiara Dalla Man.;Michael J Firbank.;Annette Lane.;Philip T English.;Claudio Cobelli.;Roy Taylor.
来源: Diabetes. 2008年57卷9期2288-95页
Hepatic triglyceride is closely associated with hepatic insulin resistance and is known to be decreased by thiazolididinediones. We studied the effect of pioglitazone on hepatic triglyceride content and the consequent effect on postprandial endogenous glucose production (EGP) in type 2 diabetes.
4266. Is the presence of retinopathy of practical value in defining cases of diabetic nephropathy in genetic association studies? The experience with the ACE insertion/deletion polymorphism in 53 studies comprising 17,791 subjects.
A key consideration when setting up genetic studies is the case definition. For diabetic nephropathy, the case definition is typically based on the presence of albuminuria. However, it has been long debated whether diabetic nephropathy cases defined in this way may have a high prevalence of nondiabetic kidney disease, especially if diabetic retinopathy is absent.
4267. Formation of composite endothelial cell-mesenchymal stem cell islets: a novel approach to promote islet revascularization.
作者: Ulrika Johansson.;Ida Rasmusson.;Simone P Niclou.;Naomi Forslund.;Linda Gustavsson.;Bo Nilsson.;Olle Korsgren.;Peetra U Magnusson.
来源: Diabetes. 2008年57卷9期2393-401页
Mesenchymal stem cells (MSCs) contribute to endothelial cell (EC) migration by producing proteases, thereby paving the way into the tissues for ECs. MSCs were added to our previously described composite EC islets as a potential means to improve their capacity for islet angiogenesis.
4268. Role of central nervous system glucagon-like Peptide-1 receptors in enteric glucose sensing.
作者: Claude Knauf.;Patrice D Cani.;Dong-Hoon Kim.;Miguel A Iglesias.;Chantal Chabo.;Aurélie Waget.;André Colom.;Sophie Rastrelli.;Nathalie M Delzenne.;Daniel J Drucker.;Randy J Seeley.;Remy Burcelin.
来源: Diabetes. 2008年57卷10期2603-12页
Ingested glucose is detected by specialized sensors in the enteric/hepatoportal vein, which send neural signals to the brain, which in turn regulates key peripheral tissues. Hence, impairment in the control of enteric-neural glucose sensing could contribute to disordered glucose homeostasis. The aim of this study was to determine the cells in the brain targeted by the activation of the enteric glucose-sensing system.
4269. Switching-on survival and repair response programs in islet transplants by bone marrow-derived vasculogenic cells.
作者: Robyn Miller.;Vincenzo Cirulli.;Giuseppe R Diaferia.;Stefania Ninniri.;Gary Hardiman.;Bruce E Torbett.;Robert Benezra.;Laura Crisa.
来源: Diabetes. 2008年57卷9期2402-12页
Vascular progenitors of bone marrow origin participate to neovascularization at sites of wound healing and transplantation. We hypothesized that the biological purpose of this bone marrow-derived vascular component is to contribute angiogenic and survival functions distinct from those provided by the local tissue-derived vasculature.
4270. Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion.
The G-protein-coupled receptor Gpr40 is expressed in beta-cells where it contributes to free fatty acid (FFA) enhancement of glucose-stimulated insulin secretion. However, other sites of Gpr40 expression, including the intestine, have been suggested. The transcription factor IPF1/PDX1 was recently shown to bind to an enhancer element within the 5'-flanking region of Gpr40, implying that IPF1/PDX1 might regulate Gpr40 expression. Here, we addressed whether 1) Gpr40 is expressed in the intestine and 2) Ipf1/Pdx1 function is required for Gpr40 expression.
4271. Pyruvate dehydrogenase kinase 4: regulation by thiazolidinediones and implication in glyceroneogenesis in adipose tissue.
作者: Thomas Cadoudal.;Emilie Distel.;Sylvie Durant.;Françoise Fouque.;Jean-Marc Blouin.;Martine Collinet.;Sylvie Bortoli.;Claude Forest.;Chantal Benelli.
来源: Diabetes. 2008年57卷9期2272-9页
Pyruvate dehydrogenase complex (PDC) serves as the metabolic switch between glucose and fatty acid utilization. PDC activity is inhibited by PDC kinase (PDK). PDC shares the same substrate, i.e., pyruvate, as glyceroneogenesis, a pathway controlling fatty acid release from white adipose tissue (WAT). Thiazolidinediones activate glyceroneogenesis. We studied the regulation by rosiglitazone of PDK2 and PDK4 isoforms and tested the hypothesis that glyceroneogenesis could be controlled by PDK.
4272. Hypothalamic protein kinase C regulates glucose production.
作者: Rachel Ross.;Penny Y T Wang.;Madhu Chari.;Carol K L Lam.;Liora Caspi.;Hiraku Ono.;Evan D Muse.;Xiaosong Li.;Roger Gutierrez-Juarez.;Peter E Light.;Gary J Schwartz.;Luciano Rossetti.;Tony K T Lam.
来源: Diabetes. 2008年57卷8期2061-5页
A selective rise in hypothalamic lipid metabolism and the subsequent activation of SUR1/Kir6.2 ATP-sensitive K(+) (K(ATP)) channels inhibit hepatic glucose production. The mechanisms that link the ability of hypothalamic lipid metabolism to the activation of K(ATP) channels remain unknown.
4273. Differential roles of cardiomyocyte and macrophage peroxisome proliferator-activated receptor gamma in cardiac fibrosis.
作者: Evren Caglayan.;Bradley Stauber.;Alan R Collins.;Christopher J Lyon.;Fen Yin.;Joey Liu.;Stephan Rosenkranz.;Erland Erdmann.;Leif E Peterson.;Robert S Ross.;Rajendra K Tangirala.;Willa A Hsueh.
来源: Diabetes. 2008年57卷9期2470-9页
Cardiac fibrosis is an important component of diabetic cardiomyopathy. Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands repress proinflammatory gene expression, including that of osteopontin, a known contributor to the development of myocardial fibrosis. We thus investigated the hypothesis that PPARgamma ligands could attenuate cardiac fibrosis.
4274. Receptor for advanced glycation end products (RAGE) deficiency attenuates the development of atherosclerosis in diabetes.
作者: Aino Soro-Paavonen.;Anna M D Watson.;Jiaze Li.;Karri Paavonen.;Audrey Koitka.;Anna C Calkin.;David Barit.;Melinda T Coughlan.;Brian G Drew.;Graeme I Lancaster.;Merlin Thomas.;Josephine M Forbes.;Peter P Nawroth.;Angelika Bierhaus.;Mark E Cooper.;Karin A Jandeleit-Dahm.
来源: Diabetes. 2008年57卷9期2461-9页
Activation of the receptor for advanced glycation end products (RAGE) in diabetic vasculature is considered to be a key mediator of atherogenesis. This study examines the effects of deletion of RAGE on the development of atherosclerosis in the diabetic apoE(-/-) model of accelerated atherosclerosis.
4277. Altered calcium homeostasis does not explain the contractile deficit of diabetic cardiomyopathy.
作者: Lin Zhang.;Mark B Cannell.;Anthony R J Phillips.;Garth J S Cooper.;Marie-Louise Ward.
来源: Diabetes. 2008年57卷8期2158-66页
This study examines the extent to which the contractile deficit of diabetic cardiomyopathy is due to altered Ca(2+) homeostasis.
4278. Pancreatic duct cells in human islet cell preparations are a source of angiogenic cytokines interleukin-8 and vascular endothelial growth factor.
作者: Babak Movahedi.;Conny Gysemans.;Daniel Jacobs-Tulleneers-Thevissen.;Chantal Mathieu.;Daniel Pipeleers.
来源: Diabetes. 2008年57卷8期2128-36页
Engraftment and function of human islet cell implants is considered to be dependent on their rapid and adequate revascularization. Studies with rodent islet grafts have shown that vascular endothelial growth factor (VEGF) expression by beta-cells can promote this process. The present work examines whether human islet preparations produce VEGF as well as interleukin (IL)-8, another angiogenic protein, and assesses the role of contaminating duct cells in VEGF and IL-8-mediated angiogenesis.
4279. CD28/CD154 blockade prevents autoimmune diabetes by inducing nondeletional tolerance after effector t-cell inhibition and regulatory T-cell expansion.
作者: Mark R Rigby.;Alison M Trexler.;Thomas C Pearson.;Christian P Larsen.
来源: Diabetes. 2008年57卷10期2672-83页
Blocking T-cell signaling is an effective means to prevent autoimmunity and allograft rejection in many animal models, yet the clinical translation of many of these approaches has not resulted in the success witnessed in experimental systems. Improved understanding of these approaches may assist in developing safe and effective means to treat disorders such as autoimmune diabetes.
4280. T-cell promiscuity in autoimmune diabetes.
It is well established that the primary mediators of beta-cell destruction in type 1 diabetes are T-cells. Nevertheless, the molecular basis for recognition of beta-cell-specific epitopes by pathogenic T-cells remains ill defined; we seek to further explore this issue.
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