Hormetic modulation of hepatic insulin sensitivity by advanced glycation end products

Author(s):Show less -

Fabre, Nelly T. ; Thieme, Karina ; Silva, Karolline S. ; Catanozi, Sergio ; Cavaleiro, Ana Mercedes ; Pinto, Jr., Danilo A. C. ; Okamoto, Maristela M. ; Morais, Mychel Raony P. T. ; Falquetto, Barbara ; Zorn, Telma M. ; Machado, Ubiratan E. ; Passarelli, Marisa ; Correa-Giannella, Maria Lucia

• Document type: Journal article
• Source: Molecular and Cellular Endocrinology; v. 447, n. C, p. 116-124, MAY 15 2017.
• Web of Science Citations: 3

Abstract

Because of the paucity of information regarding metabolic effects of advanced glycation end products (AGEs) on liver, we evaluated effects of AGEs chronic administration in (1) insulin sensitivity; (2) hepatic expression of genes involved in AGEs, glucose and fat metabolism, oxidative stress and inflammation and; (3) hepatic morphology and glycogen content. Rats received intraperitoneally albumin modified (AIbAGE) or not by advanced glycation for 12 weeks. AIbAGE induced whole-body insulin resistance concomitantly with increased hepatic insulin sensitivity, evidenced by activation of AKT, inactivation of GSK3, increased hepatic glycogen content, and decreased expression of gluconeogenesis genes. Additionally there was reduction in hepatic fat content, in expression of lipogenic, pro-inflamatory and pro oxidative genes and increase in reactive oxygen species and in nuclear expression of NRF2, a transcription factor essential to cytoprotective response. Although considered toxic, AGEs become protective when administered chronically, stimulating AKT signaling, which is involved in cellular defense and insulin sensitivity. (C) 2017 Elsevier B.V. All rights reserved. (AU)

• 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 type: Scholarships in Brazil - Doctorate
• 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 type: Scholarships in Brazil - Post-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 type: Scholarships in Brazil - Master
• FAPESP's process: 12/04831-1 - New players in glycemic control and chronic complications of Diabetes mellitus: preventive and therapeutic perspectives
• Grantee: Ubiratan Fabres Machado
• Support type: Research Projects - Thematic Grants