Molecular and functional analysis of acute LPS exposure on glycemic control in mice

Author(s)

Daniele Cristina Vitorino

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2014-08-27

Examining board members

Marcio Alberto Torsoni; Angélica Rossi Sartori Cintra; Claudio Cesar Zoppi; Leonardo dos Reis Silveira; Fernanda Ortis

• Advisor: Marcio Alberto Torsoni; Everardo Magalhães Carneiro

Abstract

The endotoxin lipopolysaccharide (LPS) is the major component of the outer membrane of Gram-negative bacteria that binds to the Toll-like receptor 4 (TLR4) inducing pro-inflammatory cytokines and mediates chronic inflammatory diseases, including obesity and diabetes. LPS chronic treatment leads to hyperglycemia, insulin resistance and compensatory insulin secretion, but its acute effects are less clear, and no studies have yet reported the effects of such treatment on one of the major process which control glucose homeostasis, the insulin clearance. Thus, the aim of the present study was to evaluate the acute LPS-induced effects on insulin clearance and insulin degrading enzyme (IDE) hepatic expression in mice. Acute LPS-treated mice showed reduce glycaemia and increased glucose tolerance, which, despite insulin resistance, could be explained by a reduced gluconeogenesis associated with increased plasma insulin. The higher insulinemia was a result of increased insulin secretion and pancreatic islets beta-cells responsiveness to glucose despite increased insulin clearance and hepatic expression of IDE. In conclusion, we demonstrated that contrary to what happens in the chronic LPS treatment, acute LPS administration actually reduces plasma glucose and increases glucose tolerance despite insulin resistance, through a combination of reduced hepatic gluconeogenesis and higher plasma insulin, and that this increased insulinemia is primarily dependent on increased insulin secretion, given that we show here that acute LPS treatment increased insulin clearance and IDE expression (AU)

• FAPESP's process: 09/16775-6 - Toll Like Receptor activation in the hypothalamus rats and the modulation of energy balance: the role of AMPK/ACC and mTOR
• Grantee: Daniele Cristina Vitorino
• Support Opportunities: Scholarships in Brazil - Doctorate