Molecular and functional analysis of the production, secretion, and action of glucagon-like peptide 1 (GLP-1) on pancreatic ²-cell function in double burden of malnutrition

• Grant number: 24/10960-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2024
• End date: September 30, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Everardo Magalhães Carneiro
• Grantee: Kênia Moreno de Oliveira
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 18/26080-4 - Characterization of molecular and functional mechanisms involved in endocrine-metabolic, cardiovascular and neural dysfunctions induced by the restriction of amino acids in vitro and in vivo: possible therapeutic role of bile acid TUDCA, AP.TEM

Abstract

The gastrointestinal tract (GI) is the entry point for food into the body and is responsible for the production of various hormones that regulate body metabolism. Among these hormones, glucagon-like peptide 1 (GLP-1) stands out, being produced not only in the intestine but also in the central nervous system (CNS) and pancreatic ±-cells. GLP-1 has insulinotropic, neogenic, and proliferative effects on pancreatic ²-cells, being crucial for the maintenance of the function and survival of this cell population. These actions can be exerted through direct stimulation via endocrine and paracrine pathways, as well as through vagal-vagal reflexes initiated in the intestine. It is known that protein restriction initiated after weaning can deleteriously program the functioning of pancreatic ²-cells, inducing changes in insulin secretion and ²-cell mass and also in parasympathetic action on this cell's function. In double burden malnutrition (DBM) models, where undernutrition and obesity coexist at different life stages, there is increased adipogenesis in response to a high-fat diet (HFD), impairment of compensatory mechanisms to HFD-induced insulin resistance, and resistance to therapeutic strategies compared to HFD consumption without prior undernutrition. Endocrine pancreatic dysfunction in mice that are either undernourished or subjected to DBM may occur due to reduced GLP-1 action on ²-cells, which, directly or indirectly, results in impaired insulin secretion and cell proliferation. Therefore, this project, by investigating GLP-1 secretion and signaling, will uniquely demonstrate how this hormone acts during DBM on the morphofunctional impairments of pancreatic ²-cells in both models.