Increasing beta-cell mass in type 2 diabetes: Does reduced NAD supply result in loss of beta-cell identity in T2D?Recipient: Dr Paul CatonInstitution: King’s College LondonCity: LondonFunding Type: Pump PrimingAmount: £20,000Description: Type 2 diabetes develops in part due to low levels of insulin release from pancreas. Previous work has shown that this can happen in type 2 diabetes because the insulin producing beta-cells change into different cell types, resulting in lower insulin secretion. This means that if we can learn how to stop beta-cells changing into other cells, or convert changed cells back to beta-cells, this could lead to the development of new drugs to treat or prevent type 2 diabetes. This study will build on our previous work to investigate whether a particular factor, called NAD, plays an important role in stopping insulin producing cells converting into other cells. If successful, new approaches which boost levels of NAD could be used as drugs to treat or prevent type 2 diabetes.
New insights into development and function of human beta-cells by gene discovery in early-onset diabetesRecipient: Dr Elisa De FrancoInstitution: University of Exeter Medical SchoolCity: ExeterFunding Type: Pump PrimingAmount: £20,000Description: We need to understand more about how the insulin-producing beta-cell works. One good way to do this is to study patients who get diabetes because they do not make insulin as a result of a single spelling mistake in one word of their whole library of books of genetic information (monogenic diabetes). These patients are likely to develop diabetes when young. We will look for the genetic cause of diabetes in patients diagnosed between 6-12 months using two recently available tools: 1) a test which allows us to select patients likely to have monogenic diabetes, this is called a genetic risk score; 2) whole-genome-sequencing which allows us to analyse the entire human DNA to identify the critical spelling mistakes in the genetic information. Using these tools we will identify the likely cause of diabetes in these children and confirm it in other patients. As we have already excluded the known causes of monogenic diabetes, this will be a new finding which will help us to understand the beta-cell better.
Comparison of metabolic coupling and insulin secretion mechanisms in mouse, pig and human isletsRecipient: Dr Attilio PingitoreInstitution: King’s College LondonCity: LondonFunding Type: Pump PrimingAmount: £19,973Description: Diabetes arises from the inability of the beta cells of the islets of Langerhans to secrete adequate amount of insulin to keep blood glucose low. Researchers have focused their attention to understanding the physiology of beta cells in order to identify new pharmacological tools or opportunities for intervention to treat diabetes. Unfortunately only a limited amount of biological islet material of human origin is available for research, thus alternative models to study human physiology are needed and they are represented mainly by islets isolated from other mammals such as mice and pigs. We will compare islets of these three species (human, pig, mouse) to identify what differences exist in terms of the mechanisms that allow increases in glucose to stimulate insulin secretion. We aim to understand what are the best conditions to work with these models in order to be able to fully translate the data obtained with Islets from mice and pigs onto human physiology.
Development of novel biological inhibitors for ketohexokinase – a target for anti-diabetic drugsRecipient: Dr Aruna AsipuInstitution: St James’s University Hospital LeedsCity: LeedsFunding Type: Pump PrimingAmount: £19,998Description: The prevalence of diabetes is increasing world-wide. Dietary studies have shown that one of the contributing factors is foods rich in fructose and sucrose, including corn syrup. How fructose increases the risk of diabetes has recently been illuminated by studies in several research laboratories. A protein (enzyme), found primarily in the liver, known as ketohexokinase, is responsible for the breakdown (metabolism) of the dietary fructose and generation of harmful products. Excessive production of these products leads to pathological changes in the body, leading to diabetes. Thus, recent research has led to the idea that blockade of ketohexokinase should help prevent high fructose diet induced diabetes. However, developing a selective small molecule drug against this enzyme is proving difficult, because KHK proteins share structural features found in a number of other important proteins in the human body. Without selectivity, small molecules are likely to cause side effects when used clinically. Here, we aim to develop new, highly specific biological molecules that may prove useful for preventing high fructose induced diabetes.
Is plasma amyloid a useful biomarker for metabolic syndrome?Recipient: Professor Michael AshfordInstitution: University of DundeeCity: DundeeFunding Type: Pump PrimingAmount: £19,664Description: The alarming increase in type 2 diabetes is primarily owing to the growing prevalence of obesity and aging. Metabolic syndrome (MetS) is a clustering of cardiovascular disease risk factors, including obesity, diabetes and high blood pressure, that affects 1 in 4 adults in the UK. It is associated with increased risk of heart disease, cancer and dementia (including Alzheimer’s disease) and death. Therefore there is a growing need for new targets in order to develop novel therapies and provide earlier diagnosis in order to provide the most effective treatment. Excessive Abeta peptide production underlies the development of Alzheimer’s disease and our recent work in mice has demonstrated a clear connection between increased Abeta production, notably the species Abeta42, and metabolic dysfunction. The major question now is whether this process is also happening in humans? Therefore we aim to determine whether serum Abeta levels can be a bio-marker for the severity of metabolic syndrome and the associated cardiovascular complications.