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Molecular mechanisms involved in the development of insulin resistance in malnutrition mice submitted to experimental obesity

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Author(s):
Thiago Martins Batista
Total Authors: 1
Document type: Doctoral Thesis
Press: Campinas, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
Defense date:
Examining board members:
Everardo Magalhães Carneiro; Fernando Abdulkader; Marcio Alberto Torsoni; Licio Augusto Velloso; Angel Nadal
Advisor: Everardo Magalhães Carneiro
Abstract

Insulin resistance is a risk factor for type 2 diabetes mellitus (T2DM) and is characterized by increased hepatic glucose output, the lower uptake of this sugar by muscle and adipose tissue and by hypersecretion of insulin by pancreatic beta cells. Population studies correlate the insufficient nutrient intake during pregnancy and early life stages with the development of insulin resistance and T2DM in adulthood. These two conditions are often associated with changes in plasma amino acid profile. Some studies show lower concentration of the sulfur-containing amino acid, taurine, in plasma of diabetic humans and mice. In this project, we investigate the development of obesity; insulin resistance and morphophysiological changes in the endocrine pancreas of mice subjected to protein restriction after weaning and then fed a high-fat diet. We also aimed to investigate the effects of taurine supplementation on the control of glucose homeostasis in this animal model. Our results show that undernourished mice respond to treatment with high fat diet similarly to mice fed a normal protein diet. Both groups became obese, hypercholesterolemic, hyperleptinemic, had higher caloric intake, increased hepatic glucose output and insulin hypersecretion in isolated islets. The taurine supplementation improved these parameters with greater intensity in mice fed a normal protein diet. These effects of taurine were associated with increased phosphorylation of thymoma viral oncogene homolog (Akt) in the liver of control mice and in malnourished mice; the phosphorylation of the AMP-activated protein kinase (AMPK) was increased. In conclusion, malnutrition after weaning doesn't accelerate nor potentiate the development of insulin resistance induced by high fat diet, but confers resistance to the effects of taurine supplementation (AU)