肠道的果糖代谢触发了类似于葡萄糖的-1-β细胞轴,以防止果糖后高糖症
Naoya Murao1,2, Yusuke Seino1,2, Risa Morikawa1
1Department of Endocrinology, Diabetes and Metabolism, Fujita Health University, School of Medicine, Toyoake, Japan.
The Journal of physiology
|October 23, 2025
概括
短期摄入果糖可以通过肠道L细胞提升胰岛素和类似葡萄糖的-1 (GLP-1),这对于预防高血糖至关重要. 这种肠-胰腺轴在肥胖的糖尿病小鼠中受损.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 肠 - 胰腺轴 肠 - 胰腺轴
- 荷尔蒙信号传递方式
背景情况:
- 果糖摄入会影响葡萄糖平衡,但涉及胰岛素和GLP-1的机制尚不清楚.
- GLP-1和GIP在调解果糖代谢作用中的作用需要进一步阐明.
- 了解L细胞对果糖的反应是代谢调节的关键.
研究的目的:
- 研究肠道L细胞中的果糖代谢如何影响GLP-1分泌.
- 确定GLP-1和GIP在摄入果糖后对胰岛素分泌和葡萄糖控制的贡献.
- 为了阐明驱动GLP-1释放以应对果糖的细胞机制.
主要方法:
- 在24小时内摄入果糖后,瘦和肥胖的糖尿病小鼠的代谢表型.
- 使用缺乏GIP受体和缺乏proglucagon的小鼠模型.
- 使用L细胞系 (GLUTag) 和与13C标记的果糖追踪隔离的肠道密室.
主要成果:
- 在小鼠中,摄入果糖会增加血胰岛素,GLP-1和GIP.
- 胰岛素对果糖的反应依赖于GLP-1,但独立于GIP.
- L细胞中的果糖代谢增加了ATP/ADP比率,关闭了KATP通道并刺激了GLP-1分泌.
结论:
- 肠道果糖代谢驱动GLP-1分泌,增强胰岛素的释放和对抗高血糖的调节.
- 一个依赖于GLP-1的肠-胰腺轴是由果糖代谢建立的.
- 这一轴在肥胖的糖尿病小鼠中受到损害,这突显了它在葡萄糖平衡中的重要性.
相关概念视频
Glucagon-like Receptor Agonists
840
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
840
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
2.2K
The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
Insulin and C-peptide are...
2.2K
Hormones Regulating Blood Glucose
6.4K
Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
In addition to accelerating glucose uptake and utilization, insulin has...
6.4K
Glucose Homeostasis: Regulation of Blood Glucose
3.8K
Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
3.8K
Hypoglycemia and Glucagon
826
Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
826
Glucose Absorption Into the Small Intestine
35.0K
Complex carbohydrates consumed cannot be absorbed into the small intestine in their original form. First, they must be hydrolyzed to a monosaccharide form such as glucose or galactose. These monosaccharides are then transported across the intestinal membrane and into the blood via transcellular transport. The intestinal epithelial cells allow the movement of these monosaccharides with a defined 'entry' through membrane transporter proteins present on their apical membrane and...
35.0K


