Metabolic control of insulin secretion in islets of Langerhans from mice submitted...
| Grant number: | 14/09532-8 |
| Support type: | Scholarships in Brazil - Post-Doctorate |
| Effective date (Start): | October 01, 2014 |
| Effective date (End): | September 30, 2018 |
| Field of knowledge: | Biological Sciences - Physiology |
| Principal Investigator: | Everardo Magalhães Carneiro |
| Grantee: | Marta García-Arévalo Provencio |
| Home Institution: | Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil |
| Associated research grant: | 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID |
Abstract Estrogen plays an essential role in the physiology of the reproductive, cardiovascular, central nervous and skeletal muscle systems. This hormone and their receptors (ERs) are also involved in energy homeostasis and glucose metabolism. They are implicated in the control of food intake, energy expenditure and white adipose tissue distribution. In the pancreatic beta cell, ERs regulate insulin mRNA content and the secretion of this hormone, as well as cell survival. Functional deregulation of ERs promotes metabolic dysfunctions increasing the predisposition to develop obesity, insulin resistance, and type 2 diabetes. Nutritional disturbances during early life are correlated with increased risk for chronic diseases at adulthood. Protein malnutrition during pregnancy, lactation or after weaning leads to impaired beta cell function through multiple mechanisms related to survival, apoptosis, calcium handling and amplification pathways. Lower insulin release is compensated with peripheral adaptations that lead to heightened insulin sensitivity. Numerous studies have shown the importance of ERs in glucose homeostasis and energy expenditure in healthy or obese individuals. However, studies on the role of these receptors in malnourished subjects and/or rodents are nonexistent. Therefore, this proposal aims to determine the expression profile of ERs and its role on the control of insulin secretion and its action in protein-malnourished mice. The mechanisms associated with estrogen signaling will be investigated in islets from protein-malnourished mice and in cell lines (beta cells, myotubules, hepatocytes) cultured in aminoacid-defficient media as a model of malnutrition in vitro. In these tissues, ERs signaling will be assessed with isoform-specific (alpha and beta) pharmacological agonists and antagonists. | |