Publications
Now showing items 4541-4560 of 5385 records
Direct endothelial nitric oxide synthase activation provides atheroprotection in diabetes-accelerated atherosclerosis
DIABETES - 01 Nov 2015
Patients with diabetes have an increased risk of developing atherosclerosis. Endothelial dysfunction, characterized by the lowered bioavailability of endothelial NO synthase (eNOS)-derived NO, is a critical inducer of atherosclerosis. However, the protective aspect of eNOS in diabetes-associated atherosclerosis remains controversial, a likely consequence of its capacity to release both protecti...
Ceramide-initiated protein phosphatase 2A activation contributes to arterial dysfunction in vivo
DIABETES - 01 Nov 2015
Prior studies have implicated accumulation of ceramide in blood vessels as a basis for vascular dysfunction in diet-induced obesity via a mechanism involving type 2 protein phosphatase (PP2A) dephosphorylation of endothelial nitric oxide synthase (eNOS). The current study sought to elucidate the mechanisms linking ceramide accumulation with PP2A activation and determine whether pharmacological ...
Inactivation of protein tyrosine phosphatases enhances interferon signaling in pancreatic islets
DIABETES - 01 Jul 2015
Type 1 diabetes (T1D) is the result of an autoimmune assault against the insulin-producing pancreatic β-cells, where chronic local inflammation (insulitis) leads to β-cell destruction. T cells and macrophages infiltrate into islets early in T1D pathogenesis. These immune cells secrete cytokines that lead to the production of reactive oxygen species (ROS) and T-cell invasion and activation. Cyto...
Bilirubin and progression of nephropathy in type 2 diabetes: a post hoc analysis of RENAAL with independent replication in IDNT
DIABETES - 01 Aug 2014
Bilirubin, a potent endogenous antioxidant, was found to protect against the development of diabetic nephropathy (DN) in rodents. In humans, cross-sectional studies found an inverse relation between bilirubin and DN. We prospectively investigated whether bilirubin is associated with progression of DN toward end-stage renal disease (ESRD). To this end, we performed a post hoc analysis in the Red...
Activating HSP72 in rodent skeletal muscle increases mitochondrial number and oxidative capacity and decreases insulin resistance
DIABETES - 01 Jun 2014
Induction of heat shock protein (HSP)72 protects against obesity-induced insulin resistance, but the underlying mechanisms are unknown. Here, we show that HSP72 plays a pivotal role in increasing skeletal muscle mitochondrial number and oxidative metabolism. Mice overexpressing HSP72 in skeletal muscle (HSP72Tg) and control wild-type (WT) mice were fed either a chow or high-fat diet (HFD). Desp...
Dicarbonyl stress in the absence of hyperglycemia increases endothelial inflammation and atherogenesis similar to that observed in diabetes
DIABETES - 01 Nov 2014
The deleterious effects of high glucose levels and enhanced metabolic flux on the vasculature are thought to be mediated by the generation of toxic metabolites, including reactive dicarbonyls like methylglyoxal (MG). In this article, we demonstrate that increasing plasma MG to levels observed in diabetic mice either using an exogenous source (1% in drinking water) or generated following inhibit...
HSP72 is a mitochondrial stress sensor critical for Parkin action, oxidative metabolism, and insulin sensitivity in skeletal muscle
DIABETES - 01 May 2014
Increased heat shock protein (HSP) 72 expression in skeletal muscle prevents obesity and glucose intolerance in mice, although the underlying mechanisms of this observation are largely unresolved. Herein we show that HSP72 is a critical regulator of stress-induced mitochondrial triage signaling since Parkin, an E3 ubiquitin ligase known to regulate mitophagy, was unable to ubiquitinate and cont...
Interleukin-18 activates skeletal muscle AMPK and reduces weight gain and insulin resistance in mice
DIABETES - 01 Sep 2013
Circulating interleukin (IL)-18 is elevated in obesity, but paradoxically causes hypophagia. We hypothesized that IL-18 may attenuate high-fat diet (HFD)-induced insulin resistance by activating AMP-activated protein kinase (AMPK). We studied mice with a global deletion of the α-isoform of the IL-18 receptor (IL-18R(-/-)) fed a standard chow or HFD. We next performed gain-of-function experiment...
Ceramides contained in LDL are elevated in type 2 diabetes and promote inflammation and skeletal muscle insulin resistance
DIABETES - 01 Feb 2013
Dysregulated lipid metabolism and inflammation are linked to the development of insulin resistance in obesity, and the intracellular accumulation of the sphingolipid ceramide has been implicated in these processes. Here, we explored the role of circulating ceramide on the pathogenesis of insulin resistance. Ceramide transported in LDL is elevated in the plasma of obese patients with type 2 diab...
Cost-effectiveness of using CYP2C19 genotype to guide selection of clopidogrel or ticagrelor in Australia
PHARMACOGENOMICS - 01 Dec 2013
AIMS:
This study aims to assess the cost-effectiveness in Australia of screening CYP2C19 loss-of-function (LoF) alleles to guide selection of clopidogrel or ticagrelor for individuals with acute coronary syndrome who are likely to undergo coronary stenting.
METHODS:
Three treatment strategies were compared: universal clopidogrel therapy, universal ticagrelor therapy and genotyping CYP2C19 wi...
Socioeconomic position and premature mortality in the AusDiab cohort of australian adults
AM J PUBLIC HEALTH - 01 Mar 2016
OBJECTIVES:
To determine the association of socioeconomic position indicators with mortality, without and with adjustment for modifiable risk factors.
METHODS:
We examined the relationships of 2 area-based indices and educational level with mortality among 9338 people (including 8094 younger than 70 years at baseline) of the Australian Diabetes Obesity and Lifestyle (AusDiab) from 1999-2000 ...
Quality of public open spaces and recreational walking
AM J PUBLIC HEALTH - 01 Dec 2015
OBJECTIVES:
We examined associations between specific public open space (POS) attributes and recreational walking to local POS.
METHODS:
Between October 2004 and December 2006, 1465 adults of the RESIDential Environments Project, conducted in Perth, Australia, reported whether they walk to a POS for recreation. For each participant, we identified all open spaces larger than 0.8 hectares ...
A framework for evaluating the impact of obesity prevention strategies on socioeconomic inequalities in weight
AM J PUBLIC HEALTH - 01 Oct 2014
We developed a theoretical framework to organize obesity prevention interventions by their likely impact on the socioeconomic gradient of weight. The degree to which an intervention involves individual agency versus structural change influences socioeconomic inequalities in weight. Agentic interventions, such as standalone social marketing, increase socioeconomic inequalities. Structural interv...
Global cardiovascular and renal outcomes of reduced GFR
J AM SOC NEPHROL - 01 Jul 2017
The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by p...
The genetic landscape of renal complications in type 1 diabetes
J AM SOC NEPHROL - 01 Feb 2017
Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-section...
Sphingomyelinase-like phosphodiesterase 3b expression levels determine podocyte injury phenotypes in glomerular disease
J AM SOC NEPHROL - 01 Jan 2015
Diabetic kidney disease (DKD) is the most common cause of ESRD in the United States. Podocyte injury is an important feature of DKD that is likely to be caused by circulating factors other than glucose. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating factor found to be elevated in the serum of patients with FSGS and causes podocyte αVβ3 integrin-dependent migration in ...
Genetic targeting or pharmacologic inhibition of NADPH oxidase nox4 provides renoprotection in long-term diabetic nephropathy
J AM SOC NEPHROL - 01 Oct 2015
Diabetic nephropathy may occur, in part, as a result of intrarenal oxidative stress. NADPH oxidases comprise the only known dedicated reactive oxygen species (ROS)-forming enzyme family. In the rodent kidney, three isoforms of the catalytic subunit of NADPH oxidase are expressed (Nox1, Nox2, and Nox4). Here we show that Nox4 is the main source of renal ROS in a mouse model of diabetic nephropat...
Nephropathy and elevated BP in mice with podocyte-specific NADPH oxidase 5 expression
J AM SOC NEPHROL - 01 Apr 2014
NADPH oxidase (Nox) enzymes are a significant source of reactive oxygen species, which contribute to glomerular podocyte dysfunction. Although studies have implicated Nox1, -2, and -4 in several glomerulopathies, including diabetic nephropathy, little is known regarding the role of Nox5 in this context. We examined Nox5 expression and regulation in kidney biopsies from diabetic patients, cultur...
Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease
J AM SOC NEPHROL - 01 Nov 2013
Diabetic kidney disease is the leading cause of ESRD, but few biomarkers of diabetic kidney disease are available. This study used gas chromatography-mass spectrometry to quantify 94 urine metabolites in screening and validation cohorts of patients with diabetes mellitus (DM) and CKD(DM+CKD), in patients with DM without CKD (DM-CKD), and in healthy controls. Compared with levels in healthy cont...
Genetic deletion of cell division autoantigen 1 retards diabetes-associated renal injury
J AM SOC NEPHROL - 01 Nov 2013
Cell division autoantigen 1 (CDA1) enhances TGF-β signaling in renal and vascular cells, and renal expression of CDA1 is elevated in animal models of diabetes. In this study, we investigated the genetic deletion of Tspyl2, the gene encoding CDA1, in C57BL6 and ApoE knockout mice. The increased renal expression of TGF-β1, TGF-β type I and II receptors, and phosphorylated Smad3 associated with di...
