SIRT1 participation in the increase of peripheral insulin sensitivity in mice fed a protein-restricted diet

Author(s)

Sarah Rickli

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2015-11-17

Examining board members

Everardo Magalhães Carneiro; Leonardo dos Reis Silveira; Edson Antunes

• Advisor: Everardo Magalhães Carneiro

Abstract

Currently, several studies have shown the relationship between the type of diet and positive or negative body adjustments, not just the short term but also long-term. In different organisms, the maintenance of homeostasis and survival depends on the ability to detect changes in nutrient levels in the external environment and adjust the intracellular biosynthesis and degradation processes. Sensing nutrients is mediated by protein kinase activity that regulate metabolic activity by phosphorylation of various substrates. Another class of sensors can alter the cellular physiology by deacetylation of specific substrates, enzymes of this class being less explored compared first. The analysis of animal protein restriction effects revealed exciting results related to sirtuins (SIRTs), a deacetilated protein family dependent of nicotinamide adenine dinucleotide (NAD +), in particular SIRT1 and protein acetylation mechanisms. About this model, still little investigated in this regard, we conclude that there are modulations of posttranslational acetylation marking that deserve to be investigated. We note that malnourished animals have changes in liver acetylation profile and in the same tissue the expression of p53, a SIRT1 target, is high. After SIRT1 activity inhibition with nicotinamide, a pharmacological inhibitor, malnourished animals showed restoration of peripheral insulin sensitivity and investigations of the molecular mechanisms concluded that the main body involved in this regulation is the muscle (AU)

• FAPESP's process: 12/25064-9 - Expression of sirtuins and its role on the control of insulin secretion in mouse pancreatic islets cultured in amino acid deficient medium
• Grantee: Sarah Rickli
• Support Opportunities: Scholarships in Brazil - Master