- 2009Pump Priming
Humanin (and related bioactive peptides) - a novel treatment for diabetic nephropathyRecipient:Dr Gavin WelshInstitution:Southmead Hospital, BristolCity:BristolAmount:£16,360Description: Diabetes is the most common cause of end stage renal failure (ESRF) in the developed world. Although the link between diabetes and kidney failure is not understood, the progression of diabetic nephropathy follows a predictable clinical course. Initially, in early diabetic nephropathy the kidneys leak small amounts of protein (microalbuminuria), and as the kidneys deteriorate further (progressive nephropathy) this amount increases (overt albuminuria). The kidney's filters consist of two cell types called podocytes and endothelial cells which interact together to form the filter. We can grow both cell types within our laboratory and the major aim of our laboratory is to understand how these cells interact and communicate with each other to form the filter in a healthy individual, and how this healthy state is disrupted during diabetes. In collaboration with Desmond Mascarenhas, (Mayflower Organization for Research & Education, Sunnyvale, CA, USA) we have become interested in the possible beneficial actions of the neuroprotective peptide humanin on the kidney. Dr. Mascarenhas has shown that this compound can markedly reduce protein loss (albuminuria) in an animal model of diabetes. This proposed work focuses on understanding the actions of humanin and other related bioactive peptides (being developed by Dr. Mascharenas) in treating the disturbances in the filtration function of the kidney seen in diabetes.
- 2009Pump Priming
Lifestyle intervention for reducing beta cell autoimmunity in type 1 diabetes: a preliminary ex-vivo studyRecipient:Dr Parth NarendranInstitution:University of BirminghamCity:BirminghamAmount:£27,000Description: Type 1 diabetes is a form of diabetes in which the insulin producing cells in the pancreas (called beta cells) are mistakenly destroyed by the body's immune system. Work we have done previously has shown that features associated with obesity bring on the onset of type 1 diabetes. This was important because it was previously generally believed that obesity was only linked to type 2 diabetes, the other common form of diabetes. We would now like to see if regular exercise in patients with type 1 diabetes can slow down immune attack of beta cells. These experiments will be preliminary, but results could form the scientific basis for a lifestyle-based approach to preventing beta cell damage in type 1 diabetes.
- 2009Pump Priming
Novel signalling pathways regulating insulin secretionRecipient:Dr Tania MaffucciInstitution:Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonCity:LondonAmount:£30,000Description: Type 2 diabetes is due to defects in production and action of insulin. Diabetes develops when pancreatic beta cells do not work properly. We still do not know precisely what goes wrong and why pancreatic beta cells release less insulin. Our work so far has suggested that pancreatic beta cells from people with type 2 diabetes possess a reduced amount of a specific protein belonging to a family of enzymes called "phosphoinositide 3-kinases" (PI3K). Furthermore our studies have revealed that when cells cultured in laboratory have reduced amount of this particular enzyme they secrete less insulin. This project wants to understand how this PI3K controls insulin secretion and the consequences of its reduction observed in diabetic individuals. This can reveal whether defects in insulin secretion observed in type 2 diabetes can be at least in part due to defect in this enzyme. This will add brand new information on how beta cells work and will help identify at least some of the steps that go wrong in type 2 diabetes, potentially leading to new treatments. It must be noted that this is the first time that a role for this enzyme in insulin secretion has been observed therefore its potential contribution to diabetes has not been investigated so far.
- 2009Pump Priming
Zinc-alpha2-glycoprotein (ZAG): A 'friend or foe' in obesity-induced insulin resistance and non-alcoholic fatty liver disease (NAFLD)Recipient:Dr Daniel CuthbertsonInstitution:University Hospital AintreeCity:LiverpoolAmount:£24,900Description: Zinc-alpha2-glycoprotein (ZAG) was first identified in cancer patients with significant weight loss. Subsequent animal experiments, whereby ZAG was either given or the levels of ZAG were manipulated genetically, demonstrated that ZAG acts as a natural regulator of the amount of fat: higher ZAG levels caused fat to be lost and burnt off, while lower ZAG levels allowed fat to accumulate. Recently, human studies have identified ZAG in fat and liver suggesting ZAG may also be relevant in controlling how much and where fat is stored in people and that it may play a role in the development of obesity, type 2 diabetes and fatty liver disease. Some reports suggest that in some people ZAG levels increase with obesity while others suggest the opposite and so its clinical relevance still remains unclear. This study aims to determine how ZAG levels change in the blood, fat and liver in people with a wide variety of body weights and to determine the effect of weight loss by examining changes in ZAG in fat and liver biopsies before and after bariatric (weight reduction) surgery. The results of the study will help us to understand how ZAG is involved in the development of obesity, type 2 diabetes and fatty liver disease, and determine whether it represents a potential target for treatment of these conditions.
- 2008Pump Priming
Analysis of the role of Munc18c tyrosine phosphorylation in insulin-stimulated glucose transportRecipient:Professor Gwyn GouldInstitution:Division of Biochemistry & Molecular Biology, Glasgow UniversityCity:GlasgowAmount:£29,747Description: Insulin stimulates glucose transport into fat and muscle by promoting the movement of specialised transporter proteins from an internal storage depot to the cell surface. These transporter proteins function as specialised doorways through which glucose can move from the blood into fat and muscle for storage after a meal. By increasing the number of 'doorways' present in the boundary membrane of cells, insulin drives glucose into storage organs. This key action of insulin is known to be impaired in type 2 diabetes, resulting in insulin resistance and aberrant glucose homeostasis. This proposal is directed towards understanding how insulin controls the insertion of these doorways into the boundary membrane.