The last few decades has seen a marked increase in the incidence of both type 1 and type 2 diabetes in Western Societies resulting in a significant individual and societal health costs. Understanding those mechanisms that contribute to the development of obesity and disorders of glucose homeostasis are therefore critical areas of research. It is increasingly recognized that the brain contributes to the development of both diabetes and obesity.
Elevated glucose at presentation with an acute coronary syndrome is associated with a poor outcome. However, clinical intervention trials have shown that normalization of glucose in the post-infarct period does not improve outcomes and may actually increase cardiovascular mortality particularly when associated with hypoglycaemia.. This studentship examines the hypothesis that hypoglycaemia in the post-infarct period induces cellular oxidative stress, and in vulnerable ischaemic tissue exacerbates myocardial damage.
The plasmalemmal sodium pump is the principal consumer of ATP in the body. In cardiac muscle, the pump is essential for normal cardiac function. In skeletal muscle, the sodium pump controls extracellular potassium concentration and therefore membrane potential and muscle fatigue. In the kidney, the ion gradients established by the pump are critical for reabsorption of water and solutes throughout the nephron, and therefore in the control of blood volume, blood pressure and cardiac load.
MAGE-A (melanoma antigen) proteins comprise a 12-member sub-family of cancer/testis antigens, so called because, physiologically, they are expressed almost exclusively in the testis, but during the development of a range of cancers (including melanoma where they were initially discovered) their expression is re-activated and is tightly associated with malignancy (i.e. with invasion and metastasis). Experimental evidence supports the idea that they are actually drivers of the malignant phenotype.
Multicellular organisms are equipped with elaborate networks of cytoprotective proteins (e.g., glutathione transferases, NAD(P)H: quinone oxidoreductase 1, heme oxygenase 1) that defend against the damaging effects of oxidants and electrophiles, the principal contributors to the pathogenesis of chronic diseases. Under basal conditions, these genes whose transcription is dependent on transcription factor Nrf2, are not expressed at their maximum capacity, but can be upregulated (induced) by a variety of synthetic and natural agents (inducers).
A high proportion of the UK population is obese and this is associated with significantly increased risk of type 2 diabetes (T2D), cardiovascular disease and Alzheimer’s disease (AD). AD is also associated with increased risk of T2D and AD patients and AD animal models demonstrate disturbances in glucose metabolism. The aspartic protease BACE1 (beta-site amyloid precursor protein (APP)-cleaving enzyme) is thought to be the primary driver for the neurodegeneration and cognitive dysfunction associated with AD.