Using crop genetics to understand the importance of dietary resistant starches for maintaining healthy glucose homeostasis

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Type 2 diabetes is a major and increasing problem worldwide and is particularly prevalent among the aging population. Over 2.5 million individuals in the UK are affected, costing the NHS around £10 billion per year (almost 10% of its budget). The risk of diabetes is thought to increase with age because of poor control of blood glucose levels. This in turn is due to a progressive decline in the capacity of cells in the pancreas (beta-cells) to secrete insulin, the hormone that controls glucose levels. The decline in beta-cell function can be accelerated by a poor diet and lifestyle, thus increasing the risk of developing type 2 diabetes. There is much evidence that diets rich in a type of carbohydrate called resistant starch have a positive impact on controlling of blood glucose levels, and hence reduce susceptibility to type 2 diabetes. Resistant starch, as the name suggests, is not completely digested in upper parts of the digestive tract, and so is fermented by bacteria in the colon. The products of fermentation, known as short-chain fatty acids, are thought to improve beta-cell function and thus insulin secretion. There are a variety of fruits and vegetables that contain various amounts of resistant starch, but UK diets are generally low in resistant starch. Thus there is great potential to reduce the incidence of type 2 diabetes in the long term by promoting the widespread consumption of resistant starch. However, very little is known about why particular types of starch are resistant to digestion and whether resistant starches from different food sources differ in their capacity to improve beta-cell function. Plugging these gaps in our knowledge will help the development of strategies to increase the amount of resistant consumed in the UK diet, thus helping to reduce the rates of onset of type 2 diabetes.Our aim is to study systematically which features of starch structure are important in making it resistant to digestion and in allowing it to improve beta cell function. As well as studying resistant starch itself, we will study the influence of the type of food in which the starch is contained, and the way in which the food is cooked prior to consumption. Our study will focus on peas, as they are a range of naturally occurring variants or mutants known to contain different types of resistant starch. These seeds, and starch extracted from them, will be digested in an artificial gut, allowing us to assess which features of the starch and the food are important for maximum fermentation in the colon. In parallel, selected types of peas will be fed to human volunteers to determine the digestibility of the starch in vivo, together with a full spectrum of short and medium term physiological responses relevant to beta-cell function and control of blood glucose levels to be monitored.We will also study the best way to process/prepare the peas, as some resistant starch can behave differently, so that they can be used in a wide range of foods. This project will provide new insights into the relationship between resistant starch and susceptibility to type 2 diabetes. Importantly it will also inform crop breeders about which genes in crop plants are associated with types of starch that provide the best protection against type 2 diabetes. This will immediately allow the directed breeding of peas that provide maximal protection against this disease. It will also increase the flexibility of peas by investigating the use of pea flour in commonly consumed foods.