Modulation of Double-Stranded RNA-Activated Protein Kinase in Insulin Sensitive Tissues of Obese Humans

被引：39

作者：

Carvalho, Bruno M. ^{[1
]}

Oliveira, Alexandre G. ^{[1
]}

Ueno, Mirian ^{[1
]}

Araujo, Tiago G. ^{[1
]}

Guadagnini, Dioze ^{[1
]}

Carvalho-Filho, Marco A. ^{[1
]}

Geloneze, Bruno ^{[1
]}

Lima, Marcelo M. O. ^{[1
]}

Pareja, Jose C. ^{[1
]}

Carvalheira, Jose B. C. ^{[1
]}

Saad, Mario J. A. ^{[1
]}

机构：

[1] Univ Estadual Campinas, Dept Internal Med, Campinas, SP, Brazil

来源：

OBESITY | 2013年 / 21卷 / 12期

基金：

巴西圣保罗研究基金会;

关键词：

Y GASTRIC BYPASS; INFLAMMATION; IMPROVEMENT; RESISTANCE; GLUCOSE; STRESS; PKR;

D O I：

10.1002/oby.20410

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: The double-stranded RNA-dependent protein kinase (PKR) was recently implicated in regulating molecular integration of nutrient- and pathogen-sensing pathways in obese mice. However, its modulation in human tissues in situations of insulin resistance has not been investigated. The present study was performed to first determine the tissue expression and phosphorylation levels of PKR in the liver, muscle, and adipose tissue in obese humans, and also the modulation of this protein in the adipose tissue of obese patients after bariatric surgery. Design and Methods: Eleven obese subjects who were scheduled to undergo Roux-en-Y Gastric Bypass Procedure participated in this study. Nine apparently healthy lean subjects as a control group were also included. Results: Our data show that PKR is activated in liver, muscle, and adipose tissue of obese humans and, after bariatric surgery, there is a clear reduction in PKR activation accompanied by a decrease in protein kinase-like endoplasmic reticulum kinase, c-Jun N-terminal kinase, inhibitor of kappa kinase, and insulin receptor substrate-1 serine 312 phosphorylation in subcutaneous adipose tissue from these patients. Conclusion: Thus, it is proposed that PKR is an important mediator of obesity-induced insulin resistance and a potential target for the therapy.

引用

页码：2452 / 2457

页数：6

共 22 条

[1] Alterations in Gastrointestinal, Endocrine, and Metabolic Processes After Bariatric Roux-en-Y Gastric Bypass Surgery [J].

Anderwald, Christian-Heinz ;

Tura, Andrea ;

Promintzer-Schifferl, Miriam ;

Prager, Gerhard ;

Stadler, Marietta ;

Ludvik, Bernhard ;

Esterbauer, Harald ;

Bischof, Martin Georg ;

Luger, Anton ;

Pacini, Giovanni ;

Krebs, Michael .

DIABETES CARE, 2012, 35 (12) :2580-2587

[2]

Araujo TG, 2012, ENDOCRINOLOGY

[3] Gastric bypass and banding equally improve insulin sensitivity and β cell function [J].

Bradley, David ;

Conte, Caterina ;

Mittendorfer, Bettina ;

Eagon, J. Christopher ;

Varela, J. Esteban ;

Fabbrini, Elisa ;

Gastaldelli, Amalia ;

Chambers, Kari T. ;

Su, Xiong ;

Okunade, Adewole ;

Patterson, Bruce W. ;

Klein, Samuel .

JOURNAL OF CLINICAL INVESTIGATION, 2012, 122 (12) :4667-4674

[4] RETRACTED: Gut Microbiota Is a Key Modulator of Insulin Resistance in TLR 2 Knockout Mice (Retracted Article) [J].

Caricilli, Andrea M. ;

Picardi, Paty K. ;

de Abreu, Lelia L. ;

Ueno, Mirian ;

Prada, Patricia O. ;

Ropelle, Eduardo R. ;

Hirabara, Sandro Massao ;

Castoldi, Angela ;

Vieira, Pedro ;

Camara, Niels O. S. ;

Curi, Rui ;

Carvalheira, Jose B. ;

Saad, Mario J. A. .

PLOS BIOLOGY, 2011, 9 (12)

[5]

Carvalho-Filho MA, 2012, ENDOCRINOLOGY

[6] The unfolded protein response in human skeletal muscle is not involved in the onset of glucose tolerance impairment induced by a fat-rich diet [J].

Deldicque, Louise ;

Van Proeyen, Karen ;

Francaux, Marc ;

Hespel, Peter .

EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY, 2011, 111 (07) :1553-1558

[7] Acute Improvement in Insulin Resistance After Laparoscopic Roux-en-Y Gastric Bypass: Is 3 Days Enough to Correct Insulin Metabolism? [J].

Faria, Gil ;

Preto, John ;

da Costa, Eduardo Lima ;

Guimaraes, Joao Tiago ;

Calhau, Conceicao ;

Taveira-Gomes, Antonio .

OBESITY SURGERY, 2013, 23 (01) :103-110

[8] Glucose homeostasis and tissue transcript content of insulin signaling intermediates in four inbred strains of mice: C57BL/6, C57BLKS/6, DBA/2, and 129X1 [J].

Goren, HJ ;

Kulkarni, RN ;

Kahn, CR .

ENDOCRINOLOGY, 2004, 145 (07) :3307-3323

[9] Inflammatory Mechanisms in Obesity [J].

Gregor, Margaret F. ;

Hotamisligil, Goekhan S. .

ANNUAL REVIEW OF IMMUNOLOGY, VOL 29, 2011, 29 :415-445

[10] Endoplasmic Reticulum Stress and Inflammation in Obesity and Diabetes [J].

Hummasti, Sarah ;

Hotamisligil, Goekhan S. .

CIRCULATION RESEARCH, 2010, 107 (05) :579-591

← 1 2 3 →