Leptin and insulin engage specific PI3K subunits in hypothalamic SF1 neurons

Cited 14 time in webofscience Cited 0 time in scopus
  • Hit : 222
  • Download : 179
Objective: The ventromedial hypothalamic nucleus (VMH) regulates energy balance and glucose homeostasis. Leptin and insulin exert metabolic effects via their cognate receptors expressed by the steroidogenic factor 1 (SF1) neurons within the VMH. However, detailed cellular mechanisms involved in the regulation of these neurons by leptin and insulin remain to be identified. Methods: We utilized genetically-modified mouse models and performed patch-clamp electrophysiology experiments to resolve this issue. Results: We identified distinct populations of leptin-activated and leptin-inhibited SF1 neurons. In contrast, insulin uniformly inhibited SF1 neurons. Notably, we found that leptin-activated, leptin-inhibited, and insulin-inhibited SF1 neurons are distinct subpopulations within the VMH. Leptin depolarization of SF1 neuron also required the PI3K p110 beta catalytic subunit. This effect was mediated by the putative transient receptor potential C (TRPC) channel. On the other hand, hyperpolarizing responses of SF1 neurons by leptin and insulin required either of the p110 alpha or p110 beta catalytic subunits, and were mediated by the putative ATP-sensitive K+ (K-ATP) channel. Conclusions: Our results demonstrate that specific PI3K catalytic subunits are responsible for the acute effects of leptin and insulin on VMH SF1 neurons, and provide insights into the cellular mechanisms of leptin and insulin action on VMH SF1 neurons that regulate energy balance and glucose homeostasis. (C) 2016 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Publisher
ELSEVIER SCIENCE BV
Issue Date
2016-08
Language
English
Article Type
Article
Keywords

PHOSPHOINOSITIDE 3-KINASE PATHWAY; VENTRAL PREMAMMILLARY NUCLEUS; PROOPIOMELANOCORTIN NEURONS; STEROIDOGENIC FACTOR-1; GLUCOSE-HOMEOSTASIS; ENERGY HOMEOSTASIS; RAPID INHIBITION; TRPC CHANNELS; MICE LACKING; OBESITY

Citation

MOLECULAR METABOLISM, v.5, no.8, pp.669 - 679

ISSN
2212-8778
DOI
10.1016/j.molmet.2016.06.004
URI
http://hdl.handle.net/10203/214851
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
98139.pdf(2.34 MB)Download
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 14 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0