Tmem117 in AVP neurons regulates the counterregulatory response to hypoglycemia.
Details
Download: 37314252_BIB_A52AA25ED9E0.pdf (4455.14 [Ko])
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_A52AA25ED9E0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Tmem117 in AVP neurons regulates the counterregulatory response to hypoglycemia.
Journal
EMBO reports
ISSN
1469-3178 (Electronic)
ISSN-L
1469-221X
Publication state
Published
Issued date
03/08/2023
Peer-reviewed
Oui
Volume
24
Number
8
Pages
e57344
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
The counterregulatory response to hypoglycemia (CRR), which ensures a sufficient glucose supply to the brain, is an essential survival function. It is orchestrated by incompletely characterized glucose-sensing neurons, which trigger a coordinated autonomous and hormonal response that restores normoglycemia. Here, we investigate the role of hypothalamic Tmem117, identified in a genetic screen as a regulator of CRR. We show that Tmem117 is expressed in vasopressin magnocellular neurons of the hypothalamus. Tmem117 inactivation in these neurons increases hypoglycemia-induced vasopressin secretion leading to higher glucagon secretion in male mice, and this effect is estrus cycle phase dependent in female mice. Ex vivo electrophysiological analysis, in situ hybridization, and in vivo calcium imaging reveal that Tmem117 inactivation does not affect the glucose-sensing properties of vasopressin neurons but increases ER stress, ROS production, and intracellular calcium levels accompanied by increased vasopressin production and secretion. Thus, Tmem117 in vasopressin neurons is a physiological regulator of glucagon secretion, which highlights the role of these neurons in the coordinated response to hypoglycemia.
Keywords
Mice, Male, Female, Animals, Glucagon/adverse effects, Calcium, Hypoglycemia/genetics, Hypoglycemia/chemically induced, Vasopressins/adverse effects, Glucose, Neurons/physiology, Blood Glucose, Insulin, Tmem117, counterregulation, glucagon, hypoglycemia, vasopressin
Pubmed
Web of science
Open Access
Yes
Create date
15/06/2023 18:00
Last modification date
09/08/2024 16:04