Dietary Protein and Amino Acid Deficiency Inhibit Pancreatic Digestive Enzyme mRNA Translation by Multiple Mechanisms.
Dietary Protein and Amino Acid Deficiency Inhibit Pancreatic Digestive Enzyme mRNA Translation by Multiple Mechanisms.
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DOI：
10.1016/j.jcmgh.2020.07.008
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发表时间：
2021
影响因子：
7.2
通讯作者：
Williams JA
中科院分区：
文献类型：
--
作者：
Sans MD;Crozier SJ;Vogel NL;D'Alecy LG;Williams JA
Chronic amino acid (AA) deficiency, as in kwashiorkor, reduces the size of the pancreas through an effect on mammalian target of rapamycin complex 1 (mTORC1). Because of the physiological importance of AAs and their role as a substrate, a stimulant of mTORC1, and protein synthesis, we studied the effect of acute protein and AA deficiency on the response to feeding. ICR/CD-1 mice were fasted overnight and refed for 2 hours with 4 different isocaloric diets: control (20% Prot); Protein-free (0% Prot); control (AA-based diet), and a leucine-free (No Leu). Protein synthesis, polysomal profiling, and the activation of several protein translation factors were analyzed in pancreas samples. All diets stimulated the Protein Kinase-B (Akt)/mTORC1 pathway, increasing the phosphorylation of the kinase Akt, the ribosomal protein S6 (S6) and the formation of the eukaryotic initiation factor 4F (eIF4F) complex. Total protein synthesis and polysome formation were inhibited in the 0% Prot and No Leu groups to a similar extent, compared with the 20% Prot group. The 0% Prot diet partially reduced the Akt/mTORC1 pathway and the activity of the guanine nucleotide exchange factor eIF2B, without affecting eIF2α phosphorylation. The No Leu diet increased the phosphorylation of eIF2α and general control nonderepressible 2, and also inhibited eIF2B activity, without affecting mTORC1. Essential and nonessential AA levels in plasma and pancreas indicated a complex regulation of their cellular transport mechanisms and their specific effect on the synthesis of digestive enzymes. These studies show that dietary AAs are important regulators of postprandial digestive enzyme synthesis, and their deficiency could induce pancreatic insufficiency and malnutrition.
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影响因子：
6.1
作者：
Bi X;Henry CJ
通讯作者：
Henry CJ
影响因子：
7.7
作者：
Floegel A;Stefan N;Yu Z;Mühlenbruch K;Drogan D;Joost HG;Fritsche A;Häring HU;Hrabě de Angelis M;Peters A;Roden M;Prehn C;Wang-Sattler R;Illig T;Schulze MB;Adamski J;Boeing H;Pischon T
通讯作者：
Pischon T
影响因子：
--
作者：
EVERSON, WV;FLAIM, KE;JEFFERSON, LS
通讯作者：
JEFFERSON, LS
DOI：
10.1152/ajpendo.91000.2008
发表时间：
2009-12-01
影响因子：
5.1
作者：
Chotechuang, Nattida;Azzout-Marniche, Dalila;Tome, Daniel
通讯作者：
Tome, Daniel
影响因子：
29.4
作者：
Crozier, Stephen J.;D'Alecy, Louis G.;Williams, John A.
通讯作者：
Williams, John A.