Hypoglycemia-Sensing Neurons of the Ventromedial Hypothalamus Require AMPK-Induced Txn2 Expression but Are Dispensable for Physiological Counterregulation
| Autor: | Salima Metref, Marc Foretz, Simon Quenneville, Davide Basco, Benoit Viollet, Gwenaël Labouèbe, Bernard Thorens |
|---|---|
| Přispěvatelé: | Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes, Paris, France |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Counterregulatory hormone
Blood Glucose medicine.medical_specialty Patch-Clamp Techniques Endocrinology Diabetes and Metabolism Hypoglycemia AMP-Activated Protein Kinases 03 medical and health sciences 0302 clinical medicine Thioredoxins Internal medicine Internal Medicine medicine Humans Protein kinase A Cells Cultured 030304 developmental biology Neurons 0303 health sciences TXN2 Chemistry AMPK [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism medicine.disease [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] medicine.anatomical_structure Ventromedial nucleus of the hypothalamus Endocrinology Glucose Metabolism nervous system Hypothalamus Ventromedial Hypothalamic Nucleus Neuron 030217 neurology & neurosurgery |
| Zdroj: | Diabetes Diabetes, American Diabetes Association, 2020, 69 (11), pp.2253-2266. ⟨10.2337/db20-0577⟩ Diabetes, vol. 69, no. 11, pp. 2253-2266 |
| ISSN: | 0012-1797 |
| Popis: | International audience; The ventromedial nucleus of the hypothalamus (VMN) is involved in the counterregulatory response to hypoglycemia. VMN neurons activated by hypoglycemia (glucose-inhibited [GI] neurons) have been assumed to play a critical although untested role in this response. Here, we show that expression of a dominant negative form of AMPK or inactivation of AMPK α1 and α2 subunit genes in Sf1 neurons of the VMN selectively suppressed GI neuron activity. We found that Txn2, encoding a mitochondrial redox enzyme, was strongly downregulated in the absence of AMPK activity and that reexpression of Txn2 in Sf1 neurons restored GI neuron activity. In cell lines, Txn2 was required to limit glucopenia-induced reactive oxygen species production. In physiological studies, absence of GI neuron activity after AMPK suppression in the VMN had no impact on the counterregulatory hormone response to hypoglycemia or on feeding. Thus, AMPK is required for GI neuron activity by controlling the expression of the antioxidant enzyme Txn2. However, the glucose-sensing capacity of VMN GI neurons is not required for the normal counterregulatory response to hypoglycemia. Instead, it may represent a fail-safe system in case of impaired hypoglycemia sensing by peripherally located glucose detection systems that are connected to the VMN. |
| Databáze: | OpenAIRE |
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