Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
School of Applied Sciences, State University of Campinas, Limeira, Brazil.
FASEB J. 2019 Nov;33(11):11909-11924. doi: 10.1096/fj.201901315R. Epub 2019 Jul 31.
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 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 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.-Furigo, I. C., de Souza, G. O., Teixeira, P. D. S., Guadagnini, D., Frazão, R., List, E. O., Kopchick, J. J., Prada, P. O., Donato, J., Jr. Growth hormone enhances the recovery of hypoglycemia ventromedial hypothalamic neurons.
生长激素(GH)在低血糖时分泌,并且在含有调节代偿性反应(CRR)的葡萄糖感应神经元的脑区域中发现了 GH 反应神经元。然而,GH 是否调节低血糖特异性神经元群体的 CRR 目前尚不清楚。研究了携带 GH 受体(GHR)在瘦素受体(LepR)或类固醇生成因子-1(SF1)表达细胞中缺失的小鼠。我们还研究了 SF1 细胞中信号转导和转录激活因子 5(STAT5)信号对 CRR 的重要性。LepR 细胞中 GHR 的缺失导致从胰岛素诱导的低血糖中恢复的能力受损,并且由 2-脱氧-D-葡萄糖(2DG)给药引起的 CRR 减弱。SF1 细胞(包括下丘脑腹内侧神经元)中 GHR 的失活也减弱了 CRR。副交感神经阻滞剂可预防降低的 CRR。此外,2DG 的输注导致副交感节前神经元的异常过度活跃,而在没有 SF1 细胞中 GHR 的小鼠中,2DG 诱导的终纹床核前神经元的激活减少。在 SF1 细胞中携带缺失的基因的小鼠在 CRR 中没有缺陷。总之,SF1 细胞中的 GHR 表达对于正常的 CRR 是必需的,并且这些作用在很大程度上独立于 STAT5 途径。-Furigo,IC,de Souza,GO,Teixeira,PD,Guadagnini,D,Frazão,R,List,EO,Kopchick,JJ,Prada,PO,Donato,Jr。生长激素增强了低血糖时下丘脑腹内侧神经元的恢复。