Fractyl Health, Inc., Lexington, MA, USA.
Diabetes Research Institute, Mills-Peninsula Medical Center, San Mateo, California.
J Diabetes Sci Technol. 2022 Nov;16(6):1567-1574. doi: 10.1177/19322968211044523. Epub 2021 Oct 26.
Modern changes in diet and lifestyle have led to an explosion of insulin resistance and metabolic diseases around the globe which, if left unchecked, will become a principal driver of morbidity and mortality in the 21st century. The nature of the metabolic homeostatic shift within the body has therefore become a topic of considerable interest. While the gut has long been recognized as an acute nutrient sensor with signaling mechanisms to the other metabolic organs of the body, its role in regulating the body's metabolic status over longer periods of time has been underappreciated. Recent insights from bariatric surgery and intestinal nutrient stimulation experiments provide a window into the adaptive role of the intestinal mucosa in a foregut/hindgut metabolic balance model that helps to define metabolic parameters within the body-informing the metabolic regulation of insulin resistance versus sensitivity, hunger versus satiety, energy utilization versus energy storage, and protection from hypoglycemia versus protection from hyperglycemia. This intestinal metabolic balance model provides an intellectual framework with which to understand the distinct roles of proximal and distal intestinal segments in metabolic regulation. The model may also aid in the development of novel disease-modifying therapies that can correct the dysregulated metabolic signals from the intestine and stem the tide of metabolic diseases in society.
现代饮食和生活方式的变化导致了胰岛素抵抗和代谢性疾病在全球范围内的爆发，如果不加以控制，它们将成为 21 世纪发病率和死亡率的主要驱动因素。因此，体内代谢稳态变化的性质已成为一个相当引人关注的话题。尽管肠道长期以来一直被认为是急性营养传感器，具有向身体其他代谢器官发出信号的机制，但它在调节身体更长时间的代谢状态方面的作用一直被低估。减肥手术和肠道营养刺激实验的最新研究结果为肠道黏膜在一个前肠/后肠代谢平衡模型中的适应性作用提供了一个窗口，该模型有助于确定体内的代谢参数，从而告知胰岛素抵抗与敏感性、饥饿与饱腹感、能量利用与能量储存、低血糖保护与高血糖保护之间的代谢调节。这个肠道代谢平衡模型为理解近端和远端肠道段在代谢调节中的不同作用提供了一个智力框架。该模型还可能有助于开发新的疾病修正疗法，这些疗法可以纠正肠道失调的代谢信号，遏制代谢性疾病在社会中的蔓延。
