Fasting-induced protein phosphatase 1 regulatory subunit contributes to postprandial blood glucose homeostasis via regulation of hepatic glycogenesis.
Fasting-induced protein phosphatase 1 regulatory subunit contributes to postprandial blood glucose homeostasis via regulation of hepatic glycogenesis.
复制标题
空腹诱导的蛋白磷酸酶 1 调节亚基通过调节肝糖生成促进餐后血糖稳态。
作者：
Luo X;Zhang Y;Ruan X;Jiang X;Zhu L;Wang X;Ding Q;Liu W;Pan Y;Wang Z;Chen Y
大多数动物在其一生中经历禁食周期。众所周知，肝脏在调节糖原代谢中起核心作用。然而，肝糖原生成是如何与禁食周期协调来控制餐后葡萄糖稳态的，这在很大程度上仍然是未知的。本研究确定了肝糖原生成与禁食周期耦合的分子机制。通过一系列的分子，细胞和动物研究，我们研究了PPP 1 R3 G，蛋白磷酸酶1（PP 1）的一个糖原靶向调节亚基，是如何参与调节肝糖原生成和葡萄糖稳态的方式密切配合禁食-进食周期。肝脏中PPP 1 R3 G在禁食期间上调，在进食后下调。PPP 1 R3 G与糖原颗粒结合，与PP 1的催化亚基相互作用，调节糖原合成酶（GS）活性。当PPP 1 R3 G在肝脏中过表达时，空腹血糖水平降低。肝脏敲低PPP 1 R3 G可降低餐后GS活性升高，减少餐后肝糖原蓄积，并减慢餐后血糖清除。PP 1的其他糖原靶向调节亚基，如PPP 1 R3 B，PPP 1 R3 C和PPP 1 R3 D，通过禁食下调，并通过肝脏中的进食增加。我们提出，PPP 1 R3 G与其他PP 1调节亚基相反的表达模式包括一个复杂的调节机制，以控制在禁食周期中的肝糖原生成。PPP 1 R3 G由于其独特的表达模式，通过其对肝糖原生成的调节，在控制禁食-进食过渡期间的餐后葡萄糖稳态中起主要作用。
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. 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. 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. 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.
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影响因子：
15.9
作者：
HWANG, JH;PERSEGHIN, G;SHULMAN, GI
通讯作者：
SHULMAN, GI
影响因子：
7.7
作者：
Delibegovic, M;Armstrong, CG;Cohen, PTW
通讯作者：
Cohen, PTW
影响因子：
3.3
作者：
LO, S;RUSSELL, JC;TAYLOR, AW
通讯作者：
TAYLOR, AW
DOI：
10.1111/j.1432-1033.1996.0570z.x
发表时间：
1996-06-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
FernandezNovell, JM;Roca, A;Guinovart, JJ
通讯作者：
Guinovart, JJ
影响因子：
5.3
作者：
Greenberg, CC;Danos, AM;Brady, MJ
通讯作者：
Brady, MJ