- 2015Pump Priming
Nogo-B in diabetic glomerulopathy: novel target for treatment?Recipient:Professor Luigi GnudiInstitution:King’s College LondonCity:LondonAmount:£20,000Description: We know that molecules that alter vascular remodelling and vascular growth have been proposed as a treatment for diabetic nephropathy. We have begun to investigate a molecule, which protects the vasculature from injury, called Nogo-B in diabetic kidney disease. We have shown that Nogo-B is found in the kidney glomeruli, and that its levels are reduced in animals with diabetic kidney disease. In this project, we will perform experiments to investigate the role of Nogo-B in diabetic kidney disease. We will study experimental animal models of diabetes in conditions of altered expression of Nogo-B. By modulating Nogo-B levels in the kidney, we will examine whether changes in Nogo-B expression confer a protection (or promote disease susceptibility). If successful, this will open for further studies on the potential targeting of Nogo-B as treatment for diabetic nephropathy.
- 2015Pump Priming
Skeletal muscle protein metabolism and insulin sensitivity in overweight individuals: Effects of meals with various fatty acid compositionsRecipient:Dr Kostas TsintzasInstitution:University of NottinghamCity:NottinghamAmount:£19,340Description: The aim of this project is to investigate whether impairment in the action of insulin to promote the use of glucose in skeletal muscle (insulin resistance), a key element in the pathogenesis of type 2 diabetes (T2D), is linked to reduced ability of muscles to synthesise new protein in response to dietary protein intake, which ultimately may compromise maintenance of muscle size and quality of life. Consumption of meals with high fat content, in particular those containing saturated fat, can cause insulin resistance, whereas liquid meals high in polyunsaturated fat content (such as fish oil) can be protective. However, little is known about the effects of high fat meals with different fat composition on muscle protein metabolism in sedentary middle-aged overweight/obese individuals, a population that is susceptible to T2D and age-related decline in skeletal muscle mass.
- 2015Pump Priming
The role of the transcriptional repressor CITED2 in endothelial cells as a mediator of impaired angiogenesis in insulin resistant conditionsRecipient:Mr Sam LockhartInstitution:Queen’s University BelfastCity:BelfastAmount:£20,000Description: People with diabetes have impaired formation of new blood vessels in the heart, legs, and other parts of the body. This is an important reason for some complications of diabetes. We have found that insulin can suppress a protein called CITED2 that has a role in limiting blood vessel growth. Therefore, increased levels of CITED2 may suppress blood vessel growth in people with type 2 diabetes in whom insulin has lost its normal effect (a condition called insulin resistance). The research proposed here aims to determine how the CITED2 gene is regulated by insulin. Furthermore, we plan to use mice with poor blood vessel formation due to insulin resistance. We want to show that we can improve blood vessel growth in these mice if we remove the CITED2 gene in vascular cells. Results from this research may indicate that CITED2 could be a future drug target for preventing diabetes complications.
- 2014Pump Priming
DECS, Diabetic Eye disease in Children Study: incidence, detection/presentation, clinical characteristics and putcomes of diabetic eye disease in childhood in the UKRecipient:Professor Jugnoo RahiInstitution:UCL Institute of Child HealthCity:LondonAmount:£19,978Description: Despite the recent and on-going increase in the frequency of childhood diabetes, little is known about childhood diabetic eye disease, particularly how common it is in the UK, how it develops, and its consequences for future vision. We propose to address this paucity of information in order to help plan the services and treatments children need to prevent visual loss and improve overall disease management. This study will provide currently unavailable data which cannot be accessed from existing routine sources. We plan a national incidence study of childhood diabetic eye disease (retinopathy / cataract) and diabetes-related visual disability, investigating variations (eg by age, gender, ethnicity), clinical characteristics, patterns of detection and short term outcomes. The cohort established by the proposed study will also enable future longer term studies of outcomes. ‘Cases’ will be ascertained through active surveillance by ophthalmologists reporting to the long-established British Ophthalmic Surveillance Unit, which has facilitated all the key recent national studies of childhood eye disorders, including studies carried out by our team (referenced below). As with our prior studies, we will establish at the outset a clinical research network comprising ophthalmologists who manage children with diabetes, as the forum for implementing the study and for translating findings into practice to directly impact on care.
- 2014Pump Priming
Does low vitamin D cause adipose tissue inflammation and insulin resistance?Recipient:Professor John WildingInstitution:University of LiverpoolCity:LiverpoolAmount:£20,000Description: Vitamin D is an important hormone which performs a number of vital functions in the body, and lack of it for a period can cause a variety of health problems, many of which relate to bone damage. However, it is common for obese individuals to have a low level of vitamin D in their blood. Research work suggests that low blood levels of vitamin D might make individuals more likely to develop type 2 diabetes, a condition in which the body’s cells become less responsive to insulin, the hormone which tells these cells to take sugar out of the blood for storage. This is why people with untreated diabetes can have dangerously high levels of sugar in their blood. Obese individuals tend to have bigger fat cells. These bigger fat cells are less responsive to insulin than normal sized cells, and also release ‘messengers’ that cause inflammation. This inflammation also makes it more difficult for insulin to work properly. We have done some research in this area already and our work has shown that vitamin D may reduce this inflammation in fat, which could ultimately make the body more sensitive to insulin, thus reducing the risk of type 2 diabetes. We also want to know if obese people have high levels in their bodies of a substance which might block vitamin D from reducing this inflammation. In this study, we shall take samples of fat from the abdomens of people who are having planned abdominal surgery, and use these fat biopsies to measure how much inflammation there is. We would also measure vitamin D levels in their blood and perform a number of non-invasive tests to determine the total body fat mass and where that fat is being stored. We would then analyse these results and be in a better position to say whether people with low vitamin D levels have more inflammation in their fat and therefore don’t respond to insulin as they should.