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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression

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Author(s):
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Pinto-Junior, Danilo C. [1] ; Silva, Karolline S. [2] ; Michalani, Maria L. [1] ; Yonamine, Caio Y. [1] ; Esteves, Joao V. [1] ; Fabre, Nelly T. [3] ; Thieme, Karina [3] ; Catanozi, Sergio [2] ; Okamoto, Maristela M. [1] ; Seraphim, Patricia M. [4] ; Correa-Giannella, Maria L. [5, 3] ; Passarelli, Marisa [2] ; Machado, Ubiratan F. [1]
Total Authors: 13
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Lab Lipides LIM 10, Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Lab Carboidrato & Radioimunoensaio LIM 18, Sao Paulo - Brazil
[4] Univ Estadual Paulista, Fac Sci & Technol, Dept Physiotherapy, Sao Paulo - Brazil
[5] Univ Nove Julho Uninove, Programa Posgrad Med, Sao Paulo - Brazil
Total Affiliations: 5
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 8, MAY 25 2018.
Web of Science Citations: 4
Abstract

Little is known about advanced glycation end products (AGEs) participation in glucose homeostasis, a process in which skeletal muscle glucose transporter GLUT4 (Scl2 alpha 4 gene) plays a key role. This study investigated (1) the in vivo and in vitro effects of AGEs on Slc2 alpha 4/GLUT4 expression in skeletal muscle of healthy rats, and (2) the potential involvement of endoplasmic reticulum and inflammatory stress in the observed regulations. For in vivo analysis, rats were treated with advanced glycated rat albumin (AGE-albumin) for 12 weeks; for in vitro analysis, soleus muscles from normal rats were incubated with bovine AGE-albumin for 2.5 to 7.5 hours. In vivo, AGE-albumin induced whole-body insulin resistance; decreased (similar to 30%) Slc2 alpha 4 mRNA and GLUT4 protein content; and increased (similar to 30%) the nuclear content of nuclear factor NF-kappa-B p50 subunit (NFKB1), and cellular content of 78 kDa glucose-regulated protein (GRP78). In vitro, incubation with AGE-albumin decreased (similar to 50%) the Slc2 alpha 4/GLUT4 content; and increased cellular content of GRP78/94, phosphorylated-IKK-alpha/beta, nuclear content of NFKB1 and RELA, and the nuclear protein binding into Slc2 alpha 4 promoter NFKB-binding site. The data reveal that AGEs impair glucose homeostasis in non-diabetic states of increased AGEs concentration; an effect that involves activation of endoplasmic reticulum-and inflammatory-stress and repression of Slc2 alpha 4/GLUT4 expression. (AU)

FAPESP's process: 12/20432-0 - INVESTIGATION OF miRNAS POTENTIALLY INVOLED IN THE SLC2A4-GLUT4 EXPRESSION REGULATION IN SKELETAL MUSCLE OF DIABETIC RATS
Grantee:João Victor Del Conti Esteves
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 16/15603-0 - Unraveling mechanisms of glycemic control and chronic complications of Diabetes mellitus: contributions to human health
Grantee:Ubiratan Fabres Machado
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 16/25155-5 - Role of neuroinflammation and histone deacetylases on mechanisms of transcription of the SLC2A4 gene in SH-SY5Y cells and hippocampal neurons of obese humans without and with diabetes
Grantee:Caio Yogi Yonamine
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 12/18724-2 - Advanced glycated albumin and insulin resistance in rats: focus on periepididimal adipose tissue and N-acetylcysteine actions
Grantee:Karolline Santana da Silva
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 13/00713-7 - Effects of chronic administration of albumin modified by advanced glycation (age) on liver tissue: characterization of histological, inflammatory and antioxidant profile
Grantee:Nelly Takashima Fabre
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 14/17251-9 - The effects of chronic administration of albumin modified by advanced glycation (AGE) on renal tissue: characterization of the inflammatory, antioxidant and epigenetic profile
Grantee:Karina Thieme
Support Opportunities: Scholarships in Brazil - Post-Doctoral