Involvement of the parasympathetic nervous system on glycemic control and pancreatic islets function in malnourished mice submitted to the high-fat diet  

Author(s)

Camila Lubaczeuski

• Document type: Doctoral Thesis
• Institution: Universidade Estadual de Campinas, Instituto de Biologia
• Defense date: 2017
• Advisor: Everardo Magalhães Carneiro

Abstract

Protein restriction in mice during early life, promotes metabolic programming in adulthood, impairing their glucose tolerance and insulin action. Parasympathetic nervous system disruption seems to be involved in this process, since increased in parasympathetic tonus and decreased in sympathetic activity was observed in metabolic programmed mice. Thus, the aim of this study was to investigate the effect of subdiaphragmatic vagotomy on glucose homeostasis through insulin and glucagon secretion and action, in metabolic programmed mice, induced by a low-protein diet early in life, followed by high fat diet (HF) in adulthood. After weaning, C57BL/6 mice were received low protein diet with 6 % of protein, composing LP group. After 4 weeks, LP group was divided in LP+HF, which started to receive high-fat diet (HF) (35% of lipids), for 8 weeks, and LP+HFvag, was submitted to the vagotomy procedure at the same time as the diet was offered. Glucose-stimulated insulin and glucagon secretion; glucose tolerance; insulin and glucagon sensitivity; plasma insulin, c-peptide and glucagonconcentration; liver insulin-degrading enzyme (IDE) protein expression and hepatic glycogen content, were evaluated. Vagotomy improved glucose tolerance and reduced insulin secretion, but did not alter adiposity and insulin sensitivity in metabolic programmed mice, compared to metabolic programmed mice. These effects were accompanied by increased in insulinemia, probably due to a diminished insulin clearance, observed in LP+HFvag group. Furthermore, LP+HF and LP+HFvag mice were more sensitive to glucagon and pyruvate, contributing to lower hepatic glycogen content. The LP+HF mice presented increased glucose-stimulated glucagon secretion in isolated islets, both in stimulatory (0.5 mM) or inhibitory (11.1 mM) conditions. Vagotomy was able to improve glucagon suppression by glucose in isolated islets and in vivo, improving glucose tolerance. In conclusion, the metabolic programmed mice, when submitted to vagotomy, showed improved glucose tolerance, associated with an increase of plasma insulin concentration as result of insulin clearance reduction and reduction on glucagonemia (AU)

• FAPESP's process: 13/25847-6 - Involvement of the autonomic nervous system upon glucose control and pancreatic islets function in malnourished mice fed a high-fat diet
• Grantee: Camila Lubaczeuski
• Support type: Scholarships in Brazil - Doctorate