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Tmem117 in AVP neurons regulates the counterregulatory response to hypoglycemia
Open accessPreprint — published as 10.15252/embr.202357344 · Paper page
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 investigated 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, an estrus cycle phase-dependent effect 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 AVP production and secretion. Thus, Tmem117 in vasopressin neurons is a physiological regulator of glucagon secretion and highlight the role of these neurons in the coordinated response to hypoglycemia.
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Metadata
- Authors
- Gaspari, S., Labouèbe, G., Picard, A., Berney, X., Sanchez-Archidona, A. R., & Thorens, B.
- Affiliations
- University of Lausanne (CH)
- Corresponding author
- Thorens, Bernard
- ORCID
- Venue
- EMBO Reports
- Publisher
- openRxiv
- Published
- 2022-10-21
- Volume
- 24
- Issue
- 8
- Pages
- e57344-e57344
- ISSN
- 1469-221X (ISSN-L)
- PMC
- PMC10398655
- OpenAlex
- W4380577134
- Cited by
- 6
- References
- 1
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- EMBO Reports (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (submittedVersion, cc-by-nc-nd)
- IRIS (submittedVersion, cc-by-nc-nd)
- Funders
- National Science Foundation (310030)
- Massachusetts Department of Agricultural Resources
- Leona M. and Harry B. Helmsley Charitable Trust
- European Federation of Pharmaceutical Industries and Associations
- European Commission (777460)
- École Polytechnique Fédérale de Lausanne
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (182496, 310030)
- H2020 European Research Council (694798)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- vasopressin neurons, hypothalamus, glucagon secretion, vasopressin release, glucose detection, endoplasmic reticulum stress, reactive oxygen species, intracellular calcium, estrous cycle, magnocellular neurons
- MeSH terms
- Animals, Blood Glucose, Calcium, Female, Glucagon, Glucose, Hypoglycemia, Insulin, Male, Membrane Proteins, Neurons, Vasopressins, Mice
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