大多數(shù)動物,，包括人類，在其一生中都不斷經(jīng)歷進(jìn)食和饑餓的周期循環(huán),。進(jìn)食后以葡萄糖為主的血糖急速上升,，而血糖得不到及時的控制則是糖尿病最主要的特征，同時餐后的高血糖也是糖尿病病人罹患心血管并發(fā)癥的主要原因,。機體有多種機制參與了餐后血糖的調(diào)控,，其中最主要的途徑是通過胰島細(xì)胞分泌胰島素,，增加機體外周組織對血糖的吸收，從而降低血糖,。
肝臟是機體最重要的代謝器官,，同時也是一個血糖的感受器官。多年前的動物實驗表明,，進(jìn)食后約三分之一的血糖能夠轉(zhuǎn)化為肝糖原,，從而儲備過多的葡萄糖。但目前尚不清楚肝臟的糖原合成如何與進(jìn)食和饑餓的循環(huán)周期相協(xié)調(diào),，以維持餐后血糖的穩(wěn)定,。
中科院上海生命科學(xué)院營養(yǎng)科學(xué)研究所陳雁課題組的博士生羅小琳等人發(fā)現(xiàn)，饑餓能在小鼠肝臟中誘導(dǎo)一個基因的表達(dá),，名為PPP1R3G,，而進(jìn)食后該基因表達(dá)則下降。進(jìn)一步的研究表明PPP1R3G是一個蛋白磷酸酶的調(diào)節(jié)亞基,，PPP1R3G的功能是把該蛋白磷酸酶錨定在糖原上,，增加糖原合成酶的活性，進(jìn)而增加糖原合成,。在小鼠實驗中,，羅小琳等人發(fā)現(xiàn)過度表達(dá)PPP1R3G后，進(jìn)食后血糖清除率明顯提高,。若在小鼠中降低PPP1R3G的表達(dá),，進(jìn)食后的血糖清除速度則顯著延遲。因此,，這一研究發(fā)現(xiàn)了肝臟PPP1R3G在餐后血糖的調(diào)控中發(fā)揮了至關(guān)重要的功能,，而尤其有意義的是，這一功能與機體的進(jìn)食和饑餓周期緊密相扣,。機體在饑餓時PPP1R3G增加,，進(jìn)食后的短時間內(nèi)，PPP1R3G可以介導(dǎo)肝糖原的快速合成,，從而快速降低血糖,。
該工作近日在國際糖尿病研究領(lǐng)域權(quán)威雜志Diabetes在線發(fā)表。血糖調(diào)控異常是糖尿病的一個最根本因素,，而糖尿病的發(fā)病率在我國以及世界范圍內(nèi)呈現(xiàn)急劇上升的趨勢,。該研究揭示了一個全新的調(diào)控餐后血糖的新機制，對于糖尿病血糖失衡的理解和未來控制血糖的策略提供了一個全新的思路,。
該工作得到了中科院、國家基金委和科技部的資助,。（生物谷Bioon.com）
生物谷推薦原文出處：
Diabetes doi: 10.2337/db10-1663
Fasting-Induced Protein Phosphatase 1 Regulatory Subunit Contributes to Postprandial Blood Glucose Homeostasis via Regulation on Hepatic Glycogenesis
Xiaolin Luo, Yongxian Zhang, Xiangbo Ruan, Xiaomeng Jiang, Lu Zhu, Xiao Wang, Qiurong Ding, Weizhong Liu, Yi Pan, Zhenzhen Wang and Yan Chen
Abstract
OBJECTIVE Most animals experience fasting–feeding cycles throughout their lives. It is well known that the liver plays a central role in regulating glycogen metabolism. However, how hepatic glycogenesis is coordinated with the fasting–feeding cycle to control postprandial glucose homeostasis remains largely unknown. This study determines the molecular mechanism underlying the coupling of hepatic glycogenesis with the fasting–feeding cycle.
RESEARCH DESIGN AND METHODS Through a series of molecular, cellular, and animal studies, we investigated how PPP1R3G, a glycogen-targeting regulatory subunit of protein phosphatase 1 (PP1), is implicated in regulating hepatic glycogenesis and glucose homeostasis in a manner tightly orchestrated with the fasting–feeding cycle.
RESULTS PPP1R3G in the liver is upregulated during fasting and downregulated after feeding. PPP1R3G associates with glycogen pellet, interacts with the catalytic subunit of PP1, and regulates glycogen synthase (GS) activity. Fasting glucose level is reduced when PPP1R3G is overexpressed in the liver. Hepatic knockdown of PPP1R3G reduces postprandial elevation of GS activity, decreases postprandial accumulation of liver glycogen, and decelerates postprandial clearance of blood glucose. Other glycogen-targeting regulatory subunits of PP1, such as PPP1R3B, PPP1R3C, and PPP1R3D, are downregulated by fasting and increased by feeding in the liver.
CONCLUSIONS We propose that the opposite expression pattern of PPP1R3G versus other PP1 regulatory subunits comprise an intricate regulatory machinery to control hepatic glycogenesis during the fasting–feeding cycle. Because of its unique expression pattern, PPP1R3G plays a major role to control postprandial glucose homeostasis during the fasting–feeding transition via its regulation on liver glycogenesis.
