Animal and plant proteins and glucose metabolism

动植物蛋白与糖代谢

• 批准号: 10089440
• 负责人: Samuel Klein
• 金额: $ 56.8万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10089440
• 关键词: Acids; Acute; Adult; Adverse effects; Aliquot; Amino Acids; Animal Structures; Animals; Biological; Biopsy; Blood Glucose; C-Peptide; Cell Wall; Chronic; Complex; Consumption; Data; Diet; Dietary Component; Dietary Intervention; Dietary Proteins; Disease; Edible Plants; FGF21 gene; Fabaceae; Food; Fortified Food; Future; GTP-Binding Proteins; Glucagon; Glucose; Glucose Clamp; Glucose Plasma Concentration; Goals; Health; Hepatic; Hormones; Human; Hyperinsulinism; Impairment; Indican; Infusion procedures; Ingestion; Insulin; Insulin Resistance; Intervention Trial; Lead; Lectin Inhibitor; Liver; Meat; Mediating; Metabolic; Metabolic dysfunction; Mus; Muscle; Non-Insulin-Dependent Diabetes Mellitus; Oral; Outcome; Participant; Plant Proteins; Plants; Plasma; Population Study; Procedures; Production; Protease Inhibitor; Proteins; Randomized; Risk; Source; Stable Isotope Labeling; Sulfate; Testing; Tracer; United States; Valine; Vascular Plant; Volatile Fatty Acids; Woman; base; blood glucose regulation; diabetes risk; glucagon-like peptide 1; glucose disposal; glucose metabolism; glucose production; improved; insulin secretion; insulin sensitivity; insulin signaling; men; microbial; obesity prevention; protein intake; protein metabolism; protein metabolite; response; stool sample; trend

Abstract Nearly 65% of adults in the United States actively try to increase their protein intake by consuming naturally protein-rich foods and foods and drinks fortified with protein isolates to improve their health. However, data from recent population studies have shown high protein consumption is associated with an increased risk of developing type 2 diabetes (T2D). This adverse effect might be specific to the type of protein consumed because several studies have found high animal protein, but not high plant protein, consumption was associated with increased T2D risk. There is experimental evidence from studies conducted in people and in mice to support a causal relationship between dietary protein intake and metabolic dysfunction. However, the effect of chronic high protein intake on glucose homeostasis and the mechanisms that cause protein-mediated metabolic dysfunction are not known. The reason(s) for the differences in the metabolic effects observed between high animal protein and high plant protein consumption are also not known, but could be due to differences in the amino acid composition and structure of animal and plant proteins per se and/or their biological matrix, which includes complex cell walls, lectins, and protease inhibitors in protein-rich plant foods, that can impair gut microbial access to proteins and/or induce the microbial production of beneficial metabolites, such as short-chain fatty acids. The goal of this proposal is to determine the effect of a high- protein diet in which the increase in protein intake is derived from different sources (animal vs plant and protein-rich whole foods vs protein isolates) on: i) liver and muscle insulin sensitivity; ii) the metabolic response to a meal, and iii) 24-h plasma concentration profiles of glucose, glucoregulatory hormones, and protein-derived metabolites purported to cause metabolic dysfunction. Our overarching hypothesis is that diets enriched with either animal or plant protein isolates, or animal protein-rich whole foods, but not plant protein-rich whole foods, cause alterations in the plasma hormones and protein metabolites that can cause insulin resistance and stimulate hepatic glucose production, thereby raising 24-h plasma glucose concentration.

摘要 近65%的美国成年人积极尝试通过增加蛋白质摄入量 食用天然富含蛋白质的食物和用分离蛋白强化的食物和饮料 改善他们的健康状况。然而，最近的人口研究数据显示，高蛋白 消费与罹患2型糖尿病(T2D)的风险增加有关。这 不良反应可能特定于摄入的蛋白质类型，因为几项研究已经 发现高动物蛋白，但不高植物蛋白，摄入与 T2D风险增加。在人类和人类中进行的研究有实验证据 小鼠支持饮食蛋白质摄入量和代谢功能障碍之间的因果关系。 然而，长期高蛋白摄入对血糖稳态的影响及其机制 导致蛋白质介导的代谢功能障碍的原因尚不清楚。原因(S) 高动物蛋白和高植物蛋白代谢效应的差异 消耗量也是未知的，但可能是由于氨基酸组成的差异 以及动植物蛋白本身和/或其生物基质的结构，包括 富含蛋白质的植物食品中可损害肠道的复杂细胞壁、凝集素和蛋白酶抑制剂 微生物获得蛋白质和/或诱导微生物产生有益代谢物， 比如短链脂肪酸。这项提案的目标是确定高- 蛋白质饮食中蛋白质摄入量的增加来自不同的来源(动物与 富含植物和蛋白质的全食与分离蛋白质)在：i)肝脏和肌肉对胰岛素的敏感性； Ii)对一餐的代谢反应，以及iii)24小时血糖的血浆浓度分布， 糖调节激素和蛋白质衍生的代谢物据称能引起代谢 功能障碍。我们的主要假设是，富含动物或植物蛋白的饮食 分离物或富含动物蛋白的全食食品，但不是富含植物蛋白的全食食品，会引起 可导致胰岛素抵抗的血浆激素和蛋白质代谢产物的变化 并刺激肝脏葡萄糖生成，从而提高24小时血糖浓度。