TRPC5 controls the adrenaline-mediated counter regulation of hypoglycemia
Hypoglycemia triggers autonomic and endocrine counter-regulatory responses to restore glucose homeostasis, a response that is impaired in patients with diabetes and its long-term complication hypoglycemia-associated autonomic failure (HAAF). We show that insulin-evoked hypoglycemia is severely aggra...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
7 October 2024
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| In: |
The EMBO journal
Year: 2024, Jahrgang: 43, Heft: 23, Pages: 5813-5836 |
| ISSN: | 1460-2075 |
| DOI: | 10.1038/s44318-024-00231-0 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s44318-024-00231-0 Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.1038/s44318-024-00231-0 
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| Verfasserangaben: | Jenny Bröker-Lai, José Rego Terol, Christin Richter, Ilka Mathar, Angela Wirth, Stefan Kopf, Ana Moreno-Pérez, Michael Büttner, Linette Liqi Tan, Mazen Makke, Gernot Poschet, Julia Hermann, Volodymyr Tsvilovskyy, Uwe Haberkorn, Philipp Wartenberg, Sebastian Susperreguy, Michael Berlin, Roger Ottenheijm, Koenraad Philippaert, Moya Wu, Tobias Wiedemann, Stephan Herzig, Anouar Belkacemi, Rebecca T Levinson, Nitin Agarwal, Juan E Camacho Londoño, Bert Klebl, Klaus Dinkel, Frank Zufall, Peter Nussbaumer, Ulrich Boehm, Rüdiger Hell, Peter Nawroth, Lutz Birnbaumer, Trese Leinders-Zufall, Rohini Kuner, Markus Zorn, Dieter Bruns, Yvonne Schwarz & Marc Freichel |
MARC
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| 245 | 1 | 0 | |a TRPC5 controls the adrenaline-mediated counter regulation of hypoglycemia |c Jenny Bröker-Lai, José Rego Terol, Christin Richter, Ilka Mathar, Angela Wirth, Stefan Kopf, Ana Moreno-Pérez, Michael Büttner, Linette Liqi Tan, Mazen Makke, Gernot Poschet, Julia Hermann, Volodymyr Tsvilovskyy, Uwe Haberkorn, Philipp Wartenberg, Sebastian Susperreguy, Michael Berlin, Roger Ottenheijm, Koenraad Philippaert, Moya Wu, Tobias Wiedemann, Stephan Herzig, Anouar Belkacemi, Rebecca T Levinson, Nitin Agarwal, Juan E Camacho Londoño, Bert Klebl, Klaus Dinkel, Frank Zufall, Peter Nussbaumer, Ulrich Boehm, Rüdiger Hell, Peter Nawroth, Lutz Birnbaumer, Trese Leinders-Zufall, Rohini Kuner, Markus Zorn, Dieter Bruns, Yvonne Schwarz & Marc Freichel |
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| 520 | |a Hypoglycemia triggers autonomic and endocrine counter-regulatory responses to restore glucose homeostasis, a response that is impaired in patients with diabetes and its long-term complication hypoglycemia-associated autonomic failure (HAAF). We show that insulin-evoked hypoglycemia is severely aggravated in mice lacking the cation channel proteins TRPC1, TRPC4, TRPC5, and TRPC6, which cannot be explained by alterations in glucagon or glucocorticoid action. By using various TRPC compound knockout mouse lines, we pinpointed the failure in sympathetic counter-regulation to the lack of the TRPC5 channel subtype in adrenal chromaffin cells, which prevents proper adrenaline rise in blood plasma. Using electrophysiological analyses, we delineate a previously unknown signaling pathway in which stimulation of PAC1 or muscarinic receptors activates TRPC5 channels in a phospholipase-C-dependent manner to induce sustained adrenaline secretion as a crucial step in the sympathetic counter response to insulin-induced hypoglycemia. By comparing metabolites in the plasma, we identified reduced taurine levels after hypoglycemia induction as a commonality in TRPC5-deficient mice and HAAF patients. | ||
| 650 | 4 | |a Adrenaline Secretion | |
| 650 | 4 | |a Calcium Signaling | |
| 650 | 4 | |a Chromaffin Cells | |
| 650 | 4 | |a Hypoglycemia Associated Autonomic Failure | |
| 650 | 4 | |a TRPC5 Channels | |
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