Growth hormone enhances the recovery of hypoglycemia via ventromedial hypothalamic neurons

Autor(es)

Furigo, Isadora C. ^[1] ; de Souza, Gabriel O. ^[1] ; Teixeira, Pryscila D. S. ^[1] ; Guadagnini, Dioze ^[2] ; Frazao, Renata ^[3] ; List, Edward O. ^{[4, 5]} ; Kopchick, John J. ^{[4, 5]} ; Prada, Patricia O. ^[2] ; Donato, Jr., Jose ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Av Prof Lineu Prestes 1524, BR-05508000 Sao Paulo - Brazil

^[2] Univ Estadual Campinas, Sch Appl Sci, Limeira - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo - Brazil

^[4] Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 - USA

^[5] Ohio Univ, Heritage Coll Osteopath Med, Athens, OH 45701 - USA

• Tipo de documento: Artigo Científico
• Fonte: FASEB JOURNAL; v. 33, n. 11, p. 11909-11924, NOV 2019.
• Citações Web of Science: 2

Resumo

Growth hormone (GH) is secreted during hypoglycemia, and GH-responsive neurons are found in brain areas containing glucose-sensing neurons that regulate the counter-regulatory response (CRR). However, whether GH modulates the CRR to hypoglycemia via specific neuronal populations is currently unknown. Mice carrying ablation of GH receptor (GHR) either in leptin receptor (LepR)- or steroidogenic factor-1 (SF1)-expressing cells were studied. We also investigated the importance of signal transducer and activator of transcription 5 (STAT5) signaling in SF1 cells for the CRR. GHR ablation in LepR cells led to impaired capacity to recover from insulin-induced hypoglycemia and to a blunted CRR caused by 2-deoxy-D-glucose (2DG) administration. GHR inactivation in SF1 cells, which include ventromedial hypothalamic neurons, also attenuated the CRR. The reduced CRR was prevented by parasympathetic blockers. Additionally, infusion of 2DG produced an abnormal hyperactivity of parasympathetic preganglionic neurons, whereas the 2DG-induced activation of anterior bed nucleus of the stria terminalis neurons was reduced in mice without GHR in SF1 cells. Mice carrying ablation of Stat5 a/b genes in SF1 cells showed no defects in the CRR. In summary, GHR expression in SF1 cells is required for a normal CRR, and these effects are largely independent of STAT5 pathway. (AU)

• Processo FAPESP: 17/02983-2 - Ação do hormônio do crescimento no sistema nervoso: relevância para as funções neurais e na doença
• Beneficiário: Jose Donato Junior
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/18498-6 - Impacto da exposição perinatal a poluentes ambientais na gênese da obesidade e diabetes mellitus tipo 2: aspectos metabólicos e epigenéticos
• Beneficiário: Patrícia de Oliveira Prada
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/20087-7 - Deleção específica de CLK2 em neurônios GABA: impacto sobre o comportamento alimentar e o metabolismo energético de camundongos
• Beneficiário: Patrícia de Oliveira Prada
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/09679-4 - Estudo dos efeitos centrais do hormônio do crescimento sobre o metabolismo energético e controle glicêmico
• Beneficiário: Isadora Clivatti Furigo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado