Direct gut to pancreas neuronal communication in the regulation of metabolism

代谢调节中肠道与胰腺神经元的直接通讯

• 批准号: BB/X017273/1
• 负责人: Kevin Murphy
• 金额: $ 77.7万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX017273%2F1
• 关键词: Direct; gut; pancreas; neuronal; communication

What you eat plays a major role in health and ill health. Every day the body consumes foods which are broken down in the gut into a complex mixture of molecules. These molecules are sensed in the gut to modulate metabolic functions. They help to regulate digestion but also body wide processes, including how the body regulates glucose, and how it processes fat and protein. New scientific tools are for the first time allowing us to understand how these food components affect metabolism and health on a molecular level. The pancreas is a particularly important metabolic organ, with critical roles in digestion, and in carbohydrate, fat and protein metabolism. Maintaining good pancreatic function is vital to maintaining health across the life course. The pancreas sits next to the upper part of the small intestine, which is called the duodenum. Almost fifty years ago it was discovered that there are neurons that originate in the wall of the duodenum which extend to the pancreas, suggesting that the gut could signal directly to the pancreas via this pathway to rapidly adjust pancreatic function and metabolism in response to food. However, subsequently, these neurons have been little studied. Our pilot data shows that a subpopulation of these neurons is involved in the pathway by which specific fats can improve the metabolic response to glucose. However, there are many other neurons in this pathway which are almost completely uncharacterised. We will map the neurons signalling from the gut to the pancreas in a mouse model, and establish the food-related molecules that regulate their function. We will manipulate these neurons in mice to determine the effects they have on metabolism, and whether they can synchronise the activity of different parts of the pancreas to have even greater effects on the body. These studies will determine whether in the future these neurons can be usefully targeted by special diets to improve long term health.

你吃的东西在健康和不健康中起着重要作用。每天身体消耗的食物在肠道中分解成复杂的分子混合物。这些分子在肠道中被感知以调节代谢功能。它们有助于调节消化，也有助于调节全身过程，包括身体如何调节葡萄糖，以及如何处理脂肪和蛋白质。新的科学工具首次使我们能够了解这些食物成分如何在分子水平上影响新陈代谢和健康。胰腺是一个特别重要的代谢器官，在消化、碳水化合物、脂肪和蛋白质代谢中起着关键作用。保持良好的胰腺功能对维持整个生命过程中的健康至关重要。胰腺位于小肠的上部，称为十二指肠。大约50年前，人们发现有起源于十二指肠壁的神经元延伸到胰腺，这表明肠道可以通过这一途径直接向胰腺发出信号，以快速调整胰腺功能和代谢以响应食物。然而，后来，这些神经元很少被研究。我们的试验数据表明，这些神经元的亚群参与了特定脂肪可以改善对葡萄糖的代谢反应的途径。然而，在这条通路中还有许多其他神经元几乎完全没有特征。我们将在小鼠模型中绘制从肠道到胰腺的神经元信号，并建立调节其功能的食物相关分子。我们将在小鼠中操纵这些神经元，以确定它们对新陈代谢的影响，以及它们是否可以同步胰腺不同部位的活动，从而对身体产生更大的影响。这些研究将确定未来这些神经元是否可以通过特殊饮食有效地靶向改善长期健康。