304 results on '"Walder, Ken"'
Search Results
302. Deficiency in interferon-gamma results in reduced body weight and better glucose tolerance in mice.
- Author
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Wong N, Fam BC, Cempako GR, Steinberg GR, Walder K, Kay TW, Proietto J, and Andrikopoulos S
- Subjects
- Animals, Gluconeogenesis, Liver metabolism, Liver Glycogen metabolism, Male, Mice, Mice, Inbred C57BL, Body Weight, Glucose metabolism, Interferon-gamma physiology
- Abstract
Obesity is a chronic low-grade inflammatory disease caused by increased energy intake and reduced energy expenditure. Studies using animal models with deletion of inflammatory cytokines have produced conflicting results with some showing increased weight gain and others showing no effect or even reduced body weights. Clearly, more work is necessary to understand the role of cytokines on body weight control. The aim of this study was to determine the effect of interferon-γ deletion (IFNγ(-/-)) on body weight regulation and glucose metabolism. Male IFNγ(-/-) and wild-type C57BL/6 mice were fed a low-fat chow diet, and body weight, food intake, and energy expenditure were monitored over 20 wk. At the end of the study, ip glucose tolerance test, insulin tolerance test, basal glucose turnover, and hyperinsulinemic/euglycemic clamps were performed. Expression levels of arcuate nucleus neuropeptide Y, Agouti-related peptide, and proopiomelanocortin mRNA as well as circulating leptin levels were also determined. IFNγ(-/-) mice had improved glucose tolerance with reduced rate of glucose appearance and increased insulin sensitivity due to greater suppression of endogenous glucose output, which was associated with decreased hepatic glucose-6-phosphatase activity. In addition, we also observed reduced body weight associated with decreased food intake and increased physical activity. Neuropeptide Y and Agouti-related peptide mRNA expression was reduced, whereas proopiomelanocortin mRNA expression was increased, as were plasma leptin levels. Global deletion of IFNγ in mice resulted in reduced body weight associated with negative energy balance, improved glucose tolerance, and hepatic insulin sensitivity. Our findings demonstrate that IFNγ plays a critical role in the regulation of body weight and glucose metabolism.
- Published
- 2011
- Full Text
- View/download PDF
303. Tanis: a link between type 2 diabetes and inflammation?
- Author
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Walder K, Kantham L, McMillan JS, Trevaskis J, Kerr L, De Silva A, Sunderland T, Godde N, Gao Y, Bishara N, Windmill K, Tenne-Brown J, Augert G, Zimmet PZ, and Collier GR
- Subjects
- Amino Acid Sequence, Animals, Apolipoproteins metabolism, Base Sequence, Blood Glucose analysis, Chromosome Mapping, Chromosomes, Human, Pair 15, Exons, Gene Expression drug effects, Gerbillinae, Glucose pharmacology, Glycosylation, Humans, Liver chemistry, Liver metabolism, Membrane Proteins chemistry, Membrane Proteins genetics, Molecular Sequence Data, Phosphorylation, Polymerase Chain Reaction, Protein Structure, Secondary, RNA, Messenger chemistry, Risk Factors, Sequence Alignment, Serum Amyloid A Protein metabolism, Diabetes Mellitus, Type 2 etiology, Inflammation etiology, Membrane Proteins physiology
- Abstract
Here we describe a novel protein, which we have named Tanis, that is implicated in type 2 diabetes and inflammation. In Psammomys obesus, a unique polygenic animal model of type 2 diabetes and the metabolic syndrome, Tanis is expressed in the liver in inverse proportion to circulating glucose (P = 0.010) and insulin levels (P = 0.004) and in direct proportion with plasma triglyceride concentrations (P = 0.007). Hepatic Tanis gene expression was markedly increased (3.1-fold) after a 24-h fast in diabetic but not in nondiabetic P. obesus. In addition, glucose inhibited Tanis gene expression in cultured hepatocytes (P = 0.006) as well as in several other cell types (P = 0.001-0.011). Thus, Tanis seems to be regulated by glucose and is dysregulated in the diabetic state. Yeast-2 hybrid screening identified serum amyloid A (SAA), an acute-phase inflammatory response protein, as an interacting protein of Tanis, and this was confirmed by Biacore experiments. SAA and other acute-phase proteins have been the focus of recent attention as risk factors for cardiovascular disease, and we contend that Tanis and its interaction with SAA may provide a mechanistic link among type 2 diabetes, inflammation, and cardiovascular disease.
- Published
- 2002
- Full Text
- View/download PDF
304. Profile of dyslipidemia in Psammomys obesus, an animal model of the metabolic syndrome.
- Author
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Walder K, Oakes N, Fahey RP, Cooney G, Zimmet PZ, and Collier GR
- Subjects
- Animals, Blood Glucose analysis, Body Weight, Cholesterol blood, Cholesterol, LDL blood, Cholesterol, VLDL blood, Chromatography, Gel, Chromatography, High Pressure Liquid, Diabetes Mellitus blood, Female, Gerbillinae, Insulin blood, Linear Models, Male, Obesity blood, Sex Characteristics, Triglycerides blood, Disease Models, Animal, Hyperlipidemias blood, Metabolic Syndrome
- Abstract
Objective: To investigate lipid profiles in Psammomys obesus and relationships between lipid profile and other components of the Metabolic Syndrome., Methods: A total number of 49 adults with a wide range of body weight and glucose tolerance were studied in a cross-sectional analysis. Plasma cholesterol distribution profiles were measured by size exclusion lipid chromatography. Blood glucose was measured using an enzymatic glucose analyser, and plasma insulin was determined by radioimmunoassay., Results: Obese diabetic Psammomys obesus had elevated plasma cholesterol (P=0.003) and triglyceride levels (p>0.001) compared to their lean littermates. The hypercholesterolemia was mainly due to increased circulating levels of VLDL-cholesterol (P=0.003) and LDL-cholesterol (P=0.003) in these animals. Multiple linear regression analyses revealed that body weight was independently associated with plasma cholesterol (P=0.011) and LDL concentration (P=0.009), while plasma insulin was associated with VLDL-cholesterol concentration (P=0.005). All of the variables measured exhibited continuous distributions across a wide range of phenotypes, from a normal rodent lipid profile to profound dyslipidemia., Conclusions: These data suggest that the dyslipidemia in obese, diabetic Psammomys obesus is closely associated with other components of the Metabolic Syndrome, including obesity and insulin resistance.
- Published
- 2002
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