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Modulation of insulin secretion by Metabolic Coupling Factors (MCFs) in pancreatic islets from undernourished obese mice: a role for chronic exercise

Grant number: 13/00750-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2013
Effective date (End): October 31, 2016
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Everardo Magalhães Carneiro
Grantee:Nayara de Carvalho Leite
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated scholarship(s):15/13929-3 - Molecular mechanisms involved in exercise training-induced adaptations on insulin secretion: a role for the ß-cell redox status, BE.EP.DR


Nowadays it is postulated that the first phase of insulin secretion is modulated by the so-called ATP-sensitive K+ channels (KATP) dependent mechanisms. The second phase of insulin secretion, markedly longer and more robust, would be modulated primarily by KATP independent mechanisms. The dependent mechanism os KATP channels corresponds to the classical pathway of insulin secretion signaling, which states that an increase in the ATP/ADP ratio, closes KATP channels, depolarizing the membrane and opening of the voltage-sensitive Ca2+ channels, triggering the exocytosis of insulin granules. On the other hand, the idependent mechanism of KATP channels modulates insulin secretion by producing metabolic coupling factors (MCFs) from mitochondrial metabolism of nutrients. Protein malnutrition reduces protein and gene expression participating from dependent and independent pathways of KATP channels, leading to a decrease in insulin secretion. On the other hand, obesity potentiates these mechanisms, increasing hormone secretion. In addition, the role of physical training in the normalization of insulin secretion has been described in both models. Low protein and high-fat diets, during important stages of development induce several changes in pancreatic islets, which impair glycemic control favoring obesity and type 2 diabetes development. However, the changes induced by the combination of these two treatments, as well as the effect of exercise in this model are unknown. Preliminary data from our group suggest that malnourished obese mice present altered insulin secretion modulated by dependent and independent KATP channels mechanisms. Thus, the aim of this project is to evaluate the control of insulin secretion by dependent and independent KATP channel pathways in malnourished obese mice subjected to chronic physical training.

Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
LEITE, Nayara de Carvalho. Mitochondrial modulation of insulin secretion : the role of protein malnutrition and physical training. 2016. Doctoral Thesis - Universidade Estadual de Campinas, Instituto de Biologia.

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