- 2015Pump Priming
Investigation of anti-insulin receptor antibodies as a potential therapy for human insulin receptoropathy.Recipient:Dr Gemma BrierleyInstitution:University of CambridgeCity:CambridgeAmount:20,000Description: Insulin works by binding to a receptor protein on the surface of cells. Certain rare mutated forms of this receptor are normally inserted into the membrane that surrounds cells, but cannot be activated by insulin. In severe cases this causes growth retardation, severe, early diabetes and usually death in childhood, and to date there has been no way to bypass the blocking effect of such receptor mutations. Antibodies that bind and activate the insulin receptor in a different way to insulin may be able to activate mutant receptors for clinical benefit, however. This project will set out to test in cell models whether particular mutations can be identified which are likely to respond to this potential treatment by assessing the effect of the antibodies on the ability of the mutant receptors to bind insulin and send signals into cells that result in metabolically relevant biological outcomes.
- 2015Pump Priming
Is high intensity interval training an efficient and effective form of exercise for people with type 1 diabetes?Recipient:Dr Sam ShepherdInstitution:Liverpool John Moores UniversityCity:LiverpoolAmount:£19,811Description: Regular exercise reduces the risk of cardiovascular disease in people with T1D and increases life expectancy. However, few people with T1D perform enough exercise to observe health benefits, citing ‘lack of time’ and worry about hypoglycaemia as the primary reasons. HIT is an exercise mode that involves repeated bouts of short (30 sec) high intensity exercise interspersed with longer periods of rest/recovery (up to 4 minutes). It takes far less time than conventional exercise, with our previous research showing greater adherence and similar health improvements as normal exercise in non-diabetics. This project will investigate whether HIT when compared to moderate-intensity exercise: a) limits the risk of hypoglycaemia following exercise, since less energy is used during HIT than normal exercise with a smaller fall in blood glucose expected, and b) improves markers of health and well-being in people with T1D.
- 2015Sutherland-Earl Clinical Fellowship
Mechanisms and prognostication of type 2 diabetes resolution following bariatric surgeryRecipient:Mr Nicholas PenneyInstitution:Imperial College LondonCity:LondonAmount:£209,164Description: Bariatric (weight loss) surgery is currently the most successful treatment for obesity. Bariatric surgery has also emerged as a highly effective treatment of type 2 diabetes in obese patients, rapidly reducing and often removing the need for patients to take diabetic medications. Interestingly, the improvement in patients’ diabetes after bariatric surgery occurs long before any significant weight loss. Through a better understanding of the reasons behind this, bariatric surgery can provide a unique 'looking glass' to identify new, non-surgical ways of treating diabetes and obesity. Recent studies have shown that bacteria within the gut play an important role in the improvement seen in patients’ diabetes. Bariatric surgery fundamentally changes the environment within the gut, which results in changes to the makeup of the trillions of bacteria living within it. These changes in the gut bacteria can affect the body in a number of complex ways, which we are only just beginning to understand. For example, gut bacteria breakdown food we are unable to absorb ourselves, leading to altered sugar levels and can release molecules that act to increase insulin sensitivity or reduce appetite. In this study I aim to characterise the changes that occur to the gut bacteria after bariatric surgery and gain a better understanding of how these changes lead to an improvement in diabetes. With this understanding I hope to discover potential targets for future treatments, such as identifying beneficial gut bacteria that could be supplemented with probiotics in patients. Additionally, although bariatric surgery is a highly successful treatment, approximately 30% of obese patients do not undergo a significant improvement in their diabetes after surgery. I aim to identify molecules (metabolites) within the patient's blood or urine that are able to predict the likely chance a patient will undergo improvement in their diabetes after bariatric surgery. This will help doctors and patients assess the likely benefit from bariatric surgery, thus enabling a personalised approach towards patient care.
- 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.