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The role of hypothalamic Growth Hormone Receptor (GHR)-expressing neurons in glycemic control

Grant number: 19/21616-6
Support type:Scholarships abroad - Research Internship - Scientific Initiation
Effective date (Start): May 01, 2020
Effective date (End): July 10, 2020
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:José Antunes Rodrigues
Grantee:Ana Luíza Romero Terra dos Santos
Supervisor abroad: Marianna Sadagurski
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Local de pesquisa : Wayne State University (WSU), United States  
Associated to the scholarship:16/19051-2 - Central relationship between oestradiol and Giot1 in osmotic regulation of ovariectomised rats, BP.IC

Abstract

In the central nervoussystem, the hypothalamus is the primary site of integration for the neuroendocrine and autonomicresponses which maintain glucose homeostasis. A state of hyperglycemia or hypoglycemia can bedetected by glucose-sensing neurons from various regions of the hypothalamus such asparaventricular (PVN), arcuate (ARC), ventromedial hypothalamus (VMH), and lateralhypothalamic area (LHA) nuclei. Activation of some of these sensors results in glucosecounterregulation. Hypothalamic GH receptor (GHR) is highly expressed in the neurons that areknown to participate in the regulation of energy balance and glucose metabolism, yet, not much isknown regarding central GHR role in these processes. Also, it has been known for decades thatsystemic glucose metabolism and hepatic glucose production is regulated by the hypothalamicagouti-related protein (AgRP)/neuropeptide Y (NPY) neuronal cluster in the ARC, however, thefunctional significance of GHR neurocircuitry in these neurons remains unclear. The proposedstudy aims to evaluate if ARC-GHR neurons are critical regulators of hepatic glucose production(HGP) especially under metabolic stress, and if GHR downstream signaling pathway specificallyin the AgRP neurons is critical for regulation of glucose homeostasis. The proposed research will,for the first time, directly address the signaling pathway of GHR activation in ARC-GHR neuronsin regulating whole-body glucose metabolism. For this, will be applied a combination ofmethodologies of post-natal neuronal-specific pharmaco-genetic knockout and systemic glucosemetabolism.