摘要
目的探讨瘦素和胰岛素调节下丘脑腹内侧核(VMH)类固醇生成因子1(SF1)神经元的结合及其机制。方法利用转基因小鼠模型进行膜片钳电生理学实验,探讨瘦素和胰岛素对VMH SF1神经元的急性作用,并确定特异性磷脂酰肌醇-3-激酶(PI3K)催化亚单位亚型(p110α和p110β)在该反应中的作用。结果瘦素可激活或抑制的SF1神经元,而胰岛素一致地抑制SF1神经元。瘦素激活、瘦素抑制和胰岛素抑制的SF1神经元是VMH内的不同亚群。SF1神经元的瘦素去极化需要PI3K p110β催化亚基。这种作用由暂时性受体电位C通道介导。另一方面,瘦素和胰岛素对SF1神经元的超极化反应需要p110α或p110β催化亚基。结论特异性PI3K催化亚单位负责了瘦素和胰岛素对VMH SF1神经元的急性作用,为瘦素和胰岛素对调节能量平衡和葡萄糖稳态的VMH SF1神经元作用的细胞机制提供科研数据。
Objective To investigate the mechanism by which leptin and insulin regulate steroidogenic factor 1(SF1)in the ventromedial hypothalamic nucleus(VMH).Method Patch clamp electrophysiological experiments were performed to investigate the acute effects of leptin and insulin on VMH SF1 neurons and to determine the role of specific phosphatidylinositolkin ase-3(PI3 K)catalytic subunit subtypes(p110αand p110β)in this reaction.Results Leptin activated or inhibited SF1 neurons,while insulin consistently inhibited SF1 neurons.SF1 neurons that were involved in leptin activation,leptin inhibition,and insulin inhibition were different subpopulations within VMH.Leptin depolarization of SF1 neurons required the PI3 K p110 beta catalytic subunit.This effect was mediated by a transient receptor potential C channel.On the other hand,hyperpolarization of SF1 neurons by leptin and insulin required a p110 alpha or p110 beta catalytic subunit.Conclusions The specific PI3 K catalytic subunit was responsible for the acute effects of leptin and insulin on VMH SF1 neurons.This observation might shield some light on the cellular mechanisms by which leptin and insulin act to regulate energy balance and glucose homeostasis in VMH SF1 neurons.
作者
李毅芳
陈丹丹
蔡燕芝
LI Yi-fang;CHEN Dan-dan;CAI Yan-zhi(Department of Endocrinology,the Second People′s Hospital of Hunan Province,Changsha,Hunan 410007,China)
出处
《热带医学杂志》
CAS
2019年第7期827-833,836,共8页
Journal of Tropical Medicine
基金
湖南省自然科学基金(2018JJ6101)
关键词
瘦素
胰岛素
条件敲除小鼠
下丘脑腹内侧核
类固醇生成因子1
Leptin
Insulin
Conditional knockout mice
Ventromedial hypothalamic nucleus
Steroid-producing factor 1
