ArticleMolecular metabolism2022
Hypothalamic Irak4 is a genetically controlled regulator of hypoglycemia-induced glucagon secretion.
Article in Molecular metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Tmem117, an oligodendrocyte-enriched regulator of NCX activity, links myelin homeostasis to counterregulation and metabolic health.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Inflammatory Cytokines Impair Glucagon Expression and Secretion in Pancreatic α-Cells.Diabetes, obesity & metabolism · 2026Article
- Liver-specific deletion of Agpat5 protects against liquid sucrose-induced hyperinsulinemia and glucose intolerance.Biochemical and biophysical research communications · 2024Article
- The Regulation and Secretion of Glucagon in Response to Nutrient Composition: Unraveling Their Intricate Mechanisms.Nutrients · 2023Review
- Article
- High-Fat Diet Aggravates the Disorder of Glucose Metabolism Caused by Chlorpyrifos Exposure in Experimental Rats.Foods (Basel, Switzerland) · 2023Article
- Cloning, distribution, and effects of growth regulation of MC3R and MC4R in red crucian carp (Frontiers in endocrinology · 2023Article
- Lipid biosynthesis enzyme Agpat5 in AgRP-neurons is required for insulin-induced hypoglycemia sensing and glucagon secretion.Nature communications · 2022Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesGlucagon secretion to stimulate hepatic glucose production is the first line of defense against hypoglycemia. This response is triggered by so far incompletely characterized central hypoglycemia-sensing mechanisms, which control autonomous nervous activity and hormone secretion. The objective of this study was to identify novel hypothalamic genes controlling insulin-induced glucagon secretion.
methodsTo obtain new information on the mechanisms of hypothalamic hypoglycemia sensing, we combined genetic and transcriptomic analysis of glucagon response to insulin-induced hypoglycemia in a panel of BXD recombinant inbred mice.
resultsWe identified two QTLs on chromosome 8 and chromosome 15. We further investigated the role of Irak4 and Cpne8, both located in the QTL on chromosome 15, in C57BL/6J and DBA/2J mice, the BXD mouse parental strains. We found that the poor glucagon response of DBA/2J mice was associated with higher hypothalamic expression of Irak4, which encodes a kinase acting downstream of the interleukin-1 receptor (Il-1R), and of Il-ß when compared with C57BL/6J mice. We showed that intracerebroventricular administration of an Il-1R antagonist in DBA/2J mice restored insulin-induced glucagon secretion; this was associated with increased c-fos expression in the arcuate and paraventricular nuclei of the hypothalamus and with higher activation of both branches of the autonomous nervous system. Whole body inactivation of Cpne8, which encodes a Ca
conclusionsCollectively, our data identify Irak4 as a genetically controlled regulator of hypoglycemia-activated hypothalamic neurons and glucagon secretion.
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