Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia.
Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia.
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DOI：
10.1172/jci163391
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发表时间：
2023-07-17
影响因子：
15.9
通讯作者：
Xu, Yong
中科院分区：
文献类型：
--
作者：
Tu, Longlong;Bean, Jonathan C.;He, Yang;Liu, Hailan;Yu, Meng;Liu, Hesong;Zhang, Nan;Yin, Na;Han, Junying;Scarcelli, Nikolas A.;Conde, Kristine M.;Wang, Mengjie;Li, Yongxiang;Feng, Bing;Gao, Peiyu;Cai, Zhao-Lin;Fukuda, Makoto;Xue, Mingshan;Tong, Qingchun;Yang, Yongjie;Liao, Lan;Xu, Jianming;Wang, Chunmei;He, Yanlin;Xu, Yong
Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons — namely, glucose-inhibited (GI) neurons — paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood glucose and impaired counterregulatory responses during hypoglycemia in mice. Activation of VMHAno4 neurons increased food intake and blood glucose, while chronic inhibition of VMHAno4 neurons ameliorated hyperglycemia in a type 1 diabetic mouse model. Finally, we showed that VMHAno4 neurons represent a unique orexigenic VMH population and transmit a positive valence, while stimulation of neurons that do not express Ano4 in the VMH (VMHnon-Ano4) suppress feeding and transmit a negative valence. Together, our results indicate that the Ano4 channel and VMHAno4 neurons are potential therapeutic targets for human diseases with abnormal feeding behavior or glucose imbalance.
影响因子：
7.7
作者：
Quenneville S;Labouèbe G;Basco D;Metref S;Viollet B;Foretz M;Thorens B
通讯作者：
Thorens B
DOI：
10.1111/j.1748-1716.2009.02005.x
发表时间：
2010-03
期刊：
Acta physiologica (Oxford, England)
影响因子：
--
作者：
Burdakov D;Lesage F
通讯作者：
Lesage F