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

2型糖尿病是世界范围内的一个主要且日益严重的问题，在老龄化人口中尤为普遍。在英国，超过250万人受到影响，NHS每年花费约100亿GB(几乎占其预算的10%)。由于血糖水平控制不佳，患糖尿病的风险被认为会随着年龄的增长而增加。这反过来又是由于胰腺细胞(β细胞)分泌胰岛素的能力逐渐下降，胰岛素是一种控制血糖水平的激素。不良的饮食和生活方式会加速β细胞功能的下降，从而增加患2型糖尿病的风险。有大量证据表明，富含一种名为抗性淀粉的碳水化合物的饮食对控制血糖水平有积极影响，因此降低了患2型糖尿病的易感性。顾名思义，抗性淀粉不会在消化道的上部完全消化，因此会被结肠中的细菌发酵。发酵的产物被称为短链脂肪酸，被认为可以改善β细胞功能，从而促进胰岛素的分泌。有多种水果和蔬菜含有不同数量的抗性淀粉，但英国人的饮食中抗性淀粉含量普遍较低。因此，通过促进抗性淀粉的广泛消费，从长远来看，降低2型糖尿病发病率的潜力很大。然而，对于为什么特定类型的淀粉对消化有抵抗力，以及来自不同食物来源的抵抗性淀粉在改善β细胞功能方面的能力是否存在差异，人们知之甚少。填补我们知识中的这些空白将有助于制定策略，增加英国饮食中消耗的抵抗力，从而有助于降低2型糖尿病的发病率。我们的目标是系统地研究淀粉结构的哪些特征对于使其抵抗消化并使其能够改善β细胞功能具有重要作用。除了研究抗性淀粉本身，我们还将研究含有淀粉的食物类型的影响，以及食物在食用前的烹调方式。我们的研究将集中在豌豆上，因为它们是一系列自然产生的变体或已知含有不同类型抗性淀粉的突变。这些种子和从中提取的淀粉将在人造肠道中被消化，使我们能够评估淀粉和食物的哪些特征对于最大限度地在结肠中发酵是重要的。同时，选定类型的豌豆将被喂给人类志愿者，以确定淀粉在体内的消化率，以及与β细胞功能和血糖水平控制相关的全部短期和中期生理反应。我们还将研究加工/准备豌豆的最佳方法，因为一些抗性淀粉可能会有不同的表现，以便它们可以用于各种食品。该项目将为抗性淀粉与2型糖尿病易感性之间的关系提供新的见解。重要的是，它还将告知作物育种者，农作物中的哪些基因与提供最佳预防2型糖尿病保护的淀粉类型有关。这将立即允许定向育种豌豆，从而最大限度地保护人们免受这种疾病的侵袭。它还将通过调查豌豆面粉在常见消费食品中的使用情况来增加豌豆的灵活性。

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.