Importance of growth hormone receptor signaling in Nos1-expressing neurons

• Grant number: 24/18534-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Jose Donato Junior
• Grantee: Marina Galleazzo Martins
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 20/01318-8 - Central nervous system as a target of growth hormone for the regulation of multiple biological functions, AP.TEM

Abstract

Growth hormone (GH) has several metabolic effects, including an anti-insulin or diabetogenic action. Consequently, excessive GH secretion induces insulin resistance and may predispose an individual to diabetes mellitus. In a study under review in PNAS, we show that ablation of the GH receptor (GHR) in Sim1-expressing cells, which include the hypothalamic paraventricular nucleus (PVH), led to a slight decrease in lean body mass without inducing changes in body adiposity. Sim1¿GHR mice exhibited reduced glycemia and a marked improvement in glucose tolerance and insulin sensitivity. Furthermore, Sim1¿GHR mice showed reduced endogenous glucose production and a robust improvement in hepatic insulin sensitivity without alterations in whole-body glucose uptake. Gene expression analysis in the PVH revealed upregulation of ATP-sensitive potassium channel subunits and reduced expression of Nos1 in Sim1¿GHR mice compared with control animals. Since a subset of neurons in the PVH expresses Nos1 and is involved in metabolic control, we hypothesize that GH action in this restricted group of neurons may mediate the diabetogenic effects of GH. Thus, the present project aims to investigate the importance of GH receptor signaling in Nos1-expressing neurons. This project is a continuation of the work already being developed in our research group and has the potential to reveal new details of how this hormone is able to control insulin sensitivity.