甘氨酸受体
甘氨酸
自分泌信号
胰岛素
内分泌学
内科学
生物
2型糖尿病
分泌物
小岛
胰岛素受体
细胞生物学
受体
糖尿病
胰岛素抵抗
生物化学
氨基酸
医学
作者
Richard Yan‐Do,Eric Duong,Jocelyn E. Manning Fox,Xiao-Qing Dai,Kunimasa Suzuki,Shara Khan,Austin Bautista,Mourad Ferdaoussi,James Lyon,Xi‐Chen Wu,Stephen Cheley,Patrick E. MacDonald,Matthias Braun
出处
期刊:Diabetes
[American Diabetes Association]
日期:2016-05-03
卷期号:65 (8): 2311-2321
被引量:62
摘要
The secretion of insulin from pancreatic islet β-cells is critical for glucose homeostasis. Disrupted insulin secretion underlies almost all forms of diabetes, including the most common form, type 2 diabetes (T2D). The control of insulin secretion is complex and affected by circulating nutrients, neuronal inputs, and local signaling. In the current study, we examined the contribution of glycine, an amino acid and neurotransmitter that activates ligand-gated Cl− currents, to insulin secretion from islets of human donors with and without T2D. We find that human islet β-cells express glycine receptors (GlyR), notably the GlyRα1 subunit, and the glycine transporter (GlyT) isoforms GlyT1 and GlyT2. β-Cells exhibit significant glycine-induced Cl− currents that promote membrane depolarization, Ca2+ entry, and insulin secretion from β-cells from donors without T2D. However, GlyRα1 expression and glycine-induced currents are reduced in β-cells from donors with T2D. Glycine is actively cleared by the GlyT expressed within β-cells, which store and release glycine that acts in an autocrine manner. Finally, a significant positive relationship exists between insulin and GlyR, because insulin enhances the glycine-activated current in a phosphoinositide 3-kinase–dependent manner, a positive feedback loop that we find is completely lost in β-cells from donors with T2D.
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