Tmem117 in AVP neurons regulates the counterregulatory response to hypoglycemia
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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.
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“…& Robert-son, 1980; Baylis et al , 1981; Chiodera et al , 1992) and that AVP stimulates GCG secretion through its binding to the AVP V1b receptor of pancreatic a cells (Dunning et al , 1984; Spruce et al , 1985; Gao et al , 1992; Yibchok-anun et al , 2004; Kim et al , 2021; Liu et al , 2021).”
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A Genetic Screen Identifies Hypothalamic Fgf15 as a Regulator of Glucagon Secretion
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- Authors
- Gaspari, S., Labouèbe, G., Picard, A., Berney, X., Rodriguez Sanchez‐Archidona, A., & Thorens, B.
- Affiliations
- University of Lausanne (CH)
- Corresponding author
- Thorens, Bernard
- Venue
- EMBO Reports
- Published
- 2023-06-14
- Volume
- 24
- Issue
- 8
- Pages
- e57344-e57344
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC10398655
- OpenAlex
- W4380577134
- Cited by
- 7
- References
- 8
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- 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
- EC | European Research Council (694798)
- EC Innovative Medicine Initiative Joint Undertaking (777460)
- SNSF | Swiss National Science Foundation (310030‐182496)
- Open access funding provided by Universite de Lausanne
- Topics
- Health Sciences › Medicine › Surgery › 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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