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4501. Critical roles for macrophages in islet angiogenesis and maintenance during pancreatic degeneration.
作者: Jeffery S Tessem.;Jan N Jensen.;Hanna Pelli.;Xu-Ming Dai.;Xiao-Hua Zong.;E Richard Stanley.;Jan Jensen.;James DeGregori.
来源: Diabetes. 2008年57卷6期1605-17页
Chronic pancreatitis, characterized by pancreatic exocrine tissue destruction with initial maintenance of islets, eventually leads to insulin-dependent diabetes in most patients. Mice deficient for the transcription factors E2F1 and E2F2 suffer from a chronic pancreatitis-like syndrome and become diabetic. Surprisingly, onset of diabetes can be prevented through bone marrow transplantation. The goal of the described studies was to determine the hematopoietic cell type responsible for maintaining islets and the associated mechanism of this protection.
4502. Having one kidney does not accelerate the rate of development of diabetic nephropathy lesions in type 1 diabetic patients.
Reduced nephron number is hypothesized to be a risk factor for chronic kidney disease and hypertension. Whether reduced nephron number accelerates the early stages of diabetic nephropathy is unknown. This study investigated whether the rate of development of diabetic nephropathy lesions was different in type 1 diabetic patients with a single (transplanted) kidney compared with patients with two (native) kidneys.
4503. Treatment of obese diabetic mice with a heme oxygenase inducer reduces visceral and subcutaneous adiposity, increases adiponectin levels, and improves insulin sensitivity and glucose tolerance.
作者: Ming Li.;Dong Hyun Kim.;Peter L Tsenovoy.;Stephen J Peterson.;Rita Rezzani.;Luigi F Rodella.;Wilbert S Aronow.;Susumu Ikehara.;Nader G Abraham.
来源: Diabetes. 2008年57卷6期1526-35页
We hypothesized that the induction of heme oxygenase (HO)-1 and increased HO activity, which induces arterial antioxidative enzymes and vasoprotection in a mouse and a rat model of diabetes, would ameliorate insulin resistance, obesity, and diabetes in the ob mouse model of type 2 diabetes.
4504. Adiponectin reduces plasma triglyceride by increasing VLDL triglyceride catabolism.
作者: Liping Qiao.;Chenhui Zou.;Deneys R van der Westhuyzen.;Jianhua Shao.
来源: Diabetes. 2008年57卷7期1824-33页
Adiponectin is an adipocyte-derived hormone that plays an important role in glucose and lipid metabolism. The main aims of this study are to investigate the effects of adiponectin on VLDL triglyceride (VLDL-TG) metabolism and the underlying mechanism.
4505. Fructose-1,6-bisphosphatase overexpression in pancreatic beta-cells results in reduced insulin secretion: a new mechanism for fat-induced impairment of beta-cell function.
作者: Melkam Kebede.;Jenny Favaloro.;Jenny E Gunton.;D Ross Laybutt.;Margaret Shaw.;Nicole Wong.;Barbara C Fam.;Kathryn Aston-Mourney.;Christian Rantzau.;Anthony Zulli.;Joseph Proietto.;Sofianos Andrikopoulos.
来源: Diabetes. 2008年57卷7期1887-95页
Fructose-1,6-bisphosphatase (FBPase) is a gluconeogenic enzyme that is upregulated in islets or pancreatic beta-cell lines exposed to high fat. However, whether specific beta-cell upregulation of FBPase can impair insulin secretory function is not known. The objective of this study therefore is to determine whether a specific increase in islet beta-cell FBPase can result in reduced glucose-mediated insulin secretion.
4506. The caspase selective inhibitor EP1013 augments human islet graft function and longevity in marginal mass islet transplantation in mice.
作者: Juliet A Emamaullee.;Joy Davis.;Rena Pawlick.;Christian Toso.;Shaheed Merani.;Sui-Xiong Cai.;Ben Tseng.;A M James Shapiro.
来源: Diabetes. 2008年57卷6期1556-66页
Clinical islet transplantation can provide insulin independence in patients with type 1 diabetes, but chronic graft failure has been observed. This has been attributed in part to loss of >or=60% of the transplanted islets in the peritransplant period, resulting in a marginal implant mass. Strategies designed to maximize survival of the initial islet mass are likely to have major impact in enhancing long-term clinical outcomes. EP1013 (N-benzyloxycabonyl-Val Asp-fluoromethyl ketone [zVD-FMK]), is a broad-spectrum caspase selective inhibitor with no observed toxicity in rodents.
4507. The diabetic phenotype in HNF4A mutation carriers is moderated by the expression of HNF4A isoforms from the P1 promoter during fetal development.
作者: Lorna W Harries.;Jonathan M Locke.;Beverley Shields.;Neil A Hanley.;Karen Piper Hanley.;Anna Steele.;Pål R Njølstad.;Sian Ellard.;Andrew T Hattersley.
来源: Diabetes. 2008年57卷6期1745-52页
Mutations in the alternatively spliced HNF4A gene cause maturity-onset diabetes of the young (MODY). We characterized the spatial and developmental expression patterns of HNF4A transcripts in human tissues and investigated their role as potential moderators of the MODY phenotype.
4508. Suppressors of cytokine-signaling proteins induce insulin resistance in the retina and promote survival of retinal cells.
作者: Xuebin Liu.;Marie G Mameza.;Yun Sang Lee.;Chikezie I Eseonu.;Cheng-Rong Yu.;Jennifer J Kang Derwent.;Charles E Egwuagu.
来源: Diabetes. 2008年57卷6期1651-8页
Suppressors of cytokine signaling (SOCS) are implicated in the etiology of diabetes, obesity, and metabolic syndrome. Here, we show that some SOCS members are induced, while others are constitutively expressed, in retina and examine whether persistent elevation of SOCS levels in retina by chronic inflammation or cellular stress predisposes to developing insulin resistance in retina, a condition implicated in diabetic retinopathy.
4509. 5-Lipoxygenase, but not 12/15-lipoxygenase, contributes to degeneration of retinal capillaries in a mouse model of diabetic retinopathy.
作者: Rose A Gubitosi-Klug.;Ramaprasad Talahalli.;Yunpeng Du.;Jerry L Nadler.;Timothy S Kern.
来源: Diabetes. 2008年57卷5期1387-93页
Lipoxygenases are regulators of chronic inflammation and oxidative stress generation. We evaluated the role of 5- and 12-lipoxygenases in the development of diabetic retinopathy.
4510. A rare mutation in ABCC8/SUR1 leading to altered ATP-sensitive K+ channel activity and beta-cell glucose sensing is associated with type 2 diabetes in adults.
作者: Andrei I Tarasov.;Tamara J Nicolson.;Jean-Pierre Riveline.;Tarvinder K Taneja.;Stephen A Baldwin.;Jocelyn M Baldwin.;Guillaume Charpentier.;Jean-François Gautier.;Philippe Froguel.;Martine Vaxillaire.;Guy A Rutter.
来源: Diabetes. 2008年57卷6期1595-604页
ATP-sensitive K(+) channels (K(ATP) channels) link glucose metabolism to the electrical activity of the pancreatic beta-cell to regulate insulin secretion. Mutations in either the Kir6.2 or sulfonylurea receptor (SUR) 1 subunit of the channel have previously been shown to cause neonatal diabetes. We describe here an activating mutation in the ABCC8 gene, encoding SUR1, that is associated with the development of type 2 diabetes only in adults.
4511. Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI.
作者: Rachel M Freathy.;Nicholas J Timpson.;Debbie A Lawlor.;Anneli Pouta.;Yoav Ben-Shlomo.;Aimo Ruokonen.;Shah Ebrahim.;Beverley Shields.;Eleftheria Zeggini.;Michael N Weedon.;Cecilia M Lindgren.;Hana Lango.;David Melzer.;Luigi Ferrucci.;Giuseppe Paolisso.;Matthew J Neville.;Fredrik Karpe.;Colin N A Palmer.;Andrew D Morris.;Paul Elliott.;Marjo-Riitta Jarvelin.;George Davey Smith.;Mark I McCarthy.;Andrew T Hattersley.;Timothy M Frayling.
来源: Diabetes. 2008年57卷5期1419-26页
Common variation in the FTO gene is associated with BMI and type 2 diabetes. Increased BMI is associated with diabetes risk factors, including raised insulin, glucose, and triglycerides. We aimed to test whether FTO genotype is associated with variation in these metabolic traits.
4512. Reduced glucocorticoid production rate, decreased 5alpha-reductase activity, and adipose tissue insulin sensitization after weight loss.
作者: Jeremy W Tomlinson.;Joanne Finney.;Beverly A Hughes.;Susan V Hughes.;Paul M Stewart.
来源: Diabetes. 2008年57卷6期1536-43页
The epidemics of obesity, insulin resistance, and type 2 diabetes have heightened the need to understand mechanisms that contribute to their pathogenesis. Increased endogenous glucocorticoid production has been implicated based on parallels with Cushing's syndrome. We have assessed the impact of weight loss on glucocorticoid secretion and metabolism (notably 11beta-hydroxysteroid dehydrogenase type 1 and 5alpha-reductase [5alphaR] activity) and insulin sensitivity.
4513. Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans.
作者: Juris J Meier.;Alexandra E Butler.;Yoshifumi Saisho.;Travis Monchamp.;Ryan Galasso.;Anil Bhushan.;Robert A Rizza.;Peter C Butler.
来源: Diabetes. 2008年57卷6期1584-94页
Little is known about the capacity, mechanisms, or timing of growth in beta-cell mass in humans. We sought to establish if the predominant expansion of beta-cell mass in humans occurs in early childhood and if, as in rodents, this coincides with relatively abundant beta-cell replication. We also sought to establish if there is a secondary growth in beta-cell mass coincident with the accelerated somatic growth in adolescence.
4514. Identification of tyrosine phosphatase 2(256-760) construct as a new, sensitive marker for the detection of islet autoimmunity in type 2 diabetic patients: the non-insulin requiring autoimmune diabetes (NIRAD) study 2.
作者: Claudio Tiberti.;Carla Giordano.;Mattia Locatelli.;Emanuele Bosi.;Gian Franco Bottazzo.;Raffaella Buzzetti.;Domenico Cucinotta.;Aldo Galluzzo.;Alberto Falorni.;Francesco Dotta.
来源: Diabetes. 2008年57卷5期1276-83页
The presence of autoantibodies to islet antigens GAD and/or tyrosine phosphatase 2 (IA-2) in type 2 diabetic patients (latent autoimmune diabetes in adults [LADA]) identifies subjects at high risk to develop insulin dependency. The aim of this study was to dissect humoral anti-IA-2 immune response in Caucasian LADA patients, identifying the most sensitive construct to evaluate IA-2 immunoreactivity and comparing LADA IA-2 epitope specificities to those found in type 1 diabetes.
4515. Kinin B1 receptor deficiency leads to leptin hypersensitivity and resistance to obesity.
作者: Marcelo A Mori.;Ronaldo C Araújo.;Felipe C G Reis.;Daniela G Sgai.;Raphael G Fonseca.;Carlos C Barros.;Vanessa F Merino.;Mariana Passadore.;Ana M Barbosa.;Bernard Ferrari.;Pierre Carayon.;Charlles H M Castro.;Suma I Shimuta.;Jacqueline Luz.;Jean-Loup Bascands.;Joost P Schanstra.;Patrick C Even.;Suzana M Oliveira.;Michael Bader.;João B Pesquero.
来源: Diabetes. 2008年57卷6期1491-500页
Kinins mediate pathophysiological processes related to hypertension, pain, and inflammation through the activation of two G-protein-coupled receptors, named B(1) and B(2). Although these peptides have been related to glucose homeostasis, their effects on energy balance are still unknown.
4516. Central nervous system neuropeptide Y signaling modulates VLDL triglyceride secretion.
作者: John M Stafford.;Fang Yu.;Richard Printz.;Alyssa H Hasty.;Larry L Swift.;Kevin D Niswender.
来源: Diabetes. 2008年57卷6期1482-90页
Elevated triglyceride (TG) is the major plasma lipid abnormality in obese and diabetic patients and contributes to cardiovascular morbidity in these disorders. We sought to identify novel mechanisms leading to hypertriglyceridemia. Resistance to negative feedback signals from adipose tissue in key central nervous system (CNS) energy homeostatic circuits contributes to the development of obesity. Because triglycerides both represent the largest energy depot in the body and are elevated in both the plasma and adipose in obesity and diabetes, we hypothesized that the same neural circuits that regulate energy balance also regulate the secretion of TGs into plasma.
4517. Elevated epidermal growth factor receptor phosphorylation induces resistance artery dysfunction in diabetic db/db mice.
作者: Souad Belmadani.;Desiree I Palen.;Romer A Gonzalez-Villalobos.;Hamid A Boulares.;Khalid Matrougui.
来源: Diabetes. 2008年57卷6期1629-37页
We previously showed epidermal growth factor receptor (EGFR) transactivation to be key mechanism in the regulation of resistance artery myogenic tone. Type 2 diabetes is associated with microvascular complications. We hypothesized that elevated EGFR phosphorylation contributes to resistance artery dysfunction in type 2 diabetes.
4518. A microsphere-based vaccine prevents and reverses new-onset autoimmune diabetes.
作者: Brett Phillips.;Karen Nylander.;Jo Harnaha.;Jennifer Machen.;Robert Lakomy.;Alexis Styche.;Kimberly Gillis.;Larry Brown.;Debra Lafreniere.;Michael Gallo.;Janet Knox.;Kenneth Hogeland.;Massimo Trucco.;Nick Giannoukakis.
来源: Diabetes. 2008年57卷6期1544-55页
This study was aimed at ascertaining the efficacy of antisense oligonucleotide-formulated microspheres to prevent type 1 diabetes and to reverse new-onset disease.
4519. Malonyl CoenzymeA decarboxylase regulates lipid and glucose metabolism in human skeletal muscle.
作者: Karim Bouzakri.;Reginald Austin.;Anna Rune.;Michael E Lassman.;Pablo M Garcia-Roves.;Joel P Berger.;Anna Krook.;Alexander V Chibalin.;Bei B Zhang.;Juleen R Zierath.
来源: Diabetes. 2008年57卷6期1508-16页
Malonyl coenzyme A (CoA) decarboxylase (MCD) is a key enzyme responsible for malonyl-CoA turnover and functions in the control of the balance between lipid and glucose metabolism. We utilized RNA interference (siRNA)-based gene silencing to determine the direct role of MCD on metabolic responses in primary human skeletal muscle.
4520. Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes.
作者: Camilla Cervin.;Valeriya Lyssenko.;Ekaterine Bakhtadze.;Eero Lindholm.;Peter Nilsson.;Tiinamaija Tuomi.;Corrado M Cilio.;Leif Groop.
来源: Diabetes. 2008年57卷5期1433-7页
Latent autoimmune diabetes in adults (LADA) is often considered a slowly progressing subtype of type 1 diabetes, although the clinical picture more resembles type 2 diabetes. One way to improve classification is to study whether LADA shares genetic features with type 1 and/or type 2 diabetes.
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