通过α细胞线粒体enolpyruvate循环的氨基酸感应调节细胞内Ca2+水平,而不影响葡萄糖分泌
Erli Jin1, Hannah R Foster1,2, Evgeniy Potapenko1,2
1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Wisconsin-Madison, Madison, WI.
Diabetes
|January 12, 2026
概括
阿尔法细胞聚酸盐循环在低血糖期间感知氨基酸. 氨酸和谷氨酸阻断氨基酸刺激的流入和葡萄糖释放,揭示了一个新的调节途径.
科学领域:
- 内分泌学 在内分泌学.
- 代谢调节 代谢调节 代谢调节
- 胰腺阿尔法细胞的功能
背景情况:
- 氨基酸是胰腺α细胞功能的关键调节剂.
- 低血糖症需要精确的葡萄糖分泌来维持葡萄糖平衡.
- 阿尔法细胞感知各种氨基酸的具体机制仍然不完全理解.
研究的目的:
- 阐明阿尔法细胞酸酸循环在氨基酸感应中的作用.
- 研究特定的氨基酸如何调节流入和葡萄糖分泌.
- 确定参与白素对α细胞活性影响的关键酶.
主要方法:
- 补丁电生理学测量KATP通道活动.
- 测量细胞内 (Ca2+) 的水平.
- 对各种氨基酸的反应中葡萄糖分泌的评估.
主要成果:
- 阿尔法细胞基酸盐循环参与在低血糖条件下感知氨基酸.
- 氨酸与谷氨酸结合时,可以抑制氨酸/氨酸刺激的Ca2+流入和葡萄糖分泌.
- 酸盐酶和酸酸碳酸酶2对于氨酸关闭α细胞KATP通道和减少Ca2+流入至关重要.
- 虽然所有测试的氨基酸都会影响葡萄糖分泌,但它们不会通过直接调节改变膜潜力或细胞内Ca2+水平.
结论:
- 阿尔法细胞醇酸盐循环在营养感应中起着重要作用,特别是在低血糖期间对氨基酸起着重要作用.
- 氨酸通过这个循环作用来抑制葡萄糖分泌,这表明营养的可用性和逆调节激素释放之间存在复杂的相互作用.
- 这些发现突出了阿尔法细胞调节中的新型分子参与者,并提供了对葡萄糖逆调节机制的见解.
相关概念视频
Feedback Regulation of Calcium Concentration
3.9K
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
3.9K
cAMP-dependent Protein Kinase Pathways
8.3K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.3K
Calmodulin-dependent Signaling
6.0K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
6.0K
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
GPCRs Regulate Adenylyl Cylase Activity
7.3K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
7.3K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
2.1K
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...
2.1K


