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一个日益严重的主要问题，在老龄化人口中尤为普遍。英国有超过250万人受到影响，每年花费约100亿英镑（几乎占其预算的10%）。由于血糖水平控制不佳，患糖尿病的风险随着年龄的增长而增加。反过来，这是由于胰腺细胞（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。有很多证据表明，富含一种叫做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，从而降低患2型糖尿病的易感性。抗性淀粉，顾名思义，在消化道的上半部分没有被完全消化，因此被结肠中的细菌发酵。发酵的产物，被称为短链脂肪酸，被认为可以改善细胞功能，从而改善胰岛素分泌。有各种各样的水果和蔬菜含有不同数量的抗性淀粉，但英国饮食中的抗性淀粉通常很低。因此，从长远来看，通过促进抗性淀粉的广泛消费，有很大的潜力来减少2型糖尿病的发病率。然而，对于为什么特定类型的淀粉具有消化抗性，以及来自不同食物来源的抗性淀粉在改善β细胞功能方面的能力是否存在差异，我们所知甚少。填补我们知识中的这些空白将有助于制定策略，以增加英国饮食中耐药的消费量，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在使其抵抗消化和使其改善β细胞功能方面是重要的。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饪方式。我们的研究将集中在豌豆上，因为它们是一系列自然发生的变种或突变体，已知含有不同类型的抗性淀粉。这些种子和从中提取的淀粉将在人工肠道中消化，这使我们能够评估淀粉和食物的哪些特征对结肠中最大程度的发酵是重要的。与此同时，选定种类的豌豆将被喂给人类志愿者，以确定体内淀粉的消化率，以及与β细胞功能和血糖水平控制相关的全方位短期和中期生理反应。我们还将研究处理/准备豌豆的最佳方法，因为一些抗性淀粉会表现不同，因此它们可以用于各种食物。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，它还将告诉作物育种者，作物中哪些基因与淀粉类型有关，而淀粉类型可以提供最好的预防2型糖尿病的保护。这将立即允许有针对性地培育能够最大限度地预防这种疾病的豌豆。它还将通过调查在常见食品中使用豌豆粉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.