TRPC3 regulates islet beta-cell insulin secretion
Abstract: Insulin release is tightly controlled by glucose-stimulated calcium (GSCa) through hitherto equivocal pathways. This study investigates TRPC3, a non-selective cation channel, as a critical regulator of insulin secretion and glucose control. TRPC3’s involvement in glucose-stimulated insu...
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| Formato: | Artículo |
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Wiley
2023
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| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/16494 |
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I33-R139-123456789-16494 |
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I33-R139-123456789-164942023-11-23T17:54:43Z TRPC3 regulates islet beta-cell insulin secretion Rached, Gaëlle Saliba, Youakim Maddah, Dina Hajal, Joelle Smayra, Viviane Bakhos, Jules Joel Groschner, Klaus Birnbaumer, Lutz Farès, Nassim TRPC3 INSULINA GLUCOSA CANALES CATIONICOS PROTEINA RECEPTORA TRANSITORIA 3 CELULAS BETA Abstract: Insulin release is tightly controlled by glucose-stimulated calcium (GSCa) through hitherto equivocal pathways. This study investigates TRPC3, a non-selective cation channel, as a critical regulator of insulin secretion and glucose control. TRPC3’s involvement in glucose-stimulated insulin secretion (GSIS) is studied in human and animal islets. TRPC3-dependent in vivo insulin secretion is investigated using pharmacological tools and Trpc3−/− mice. TRPC3’s involvement in islet glucose uptake and GSCa is explored using fluorescent glucose analogue 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose and calcium imaging. TRPC3 modulation by a small-molecule activator, GSK1702934A, is evaluated in type 2 diabetic mice. TRPC3 is functionally expressed in human and mouse islet beta cells. TRPC3-controlled insulin secretion is KATP-independent and primarily mediated by diacylglycerol channel regulation of the cytosolic calcium oscillations following glucose stimulation. Conversely, glucose uptake in islets is independent of TRPC3. TRPC3 pharmacologic inhibition and knockout in mice lead to defective insulin secretion and glucose intolerance. Subsequently, TRPC3 activation through targeted small-molecule enhances insulin secretion and alleviates diabetes hallmarks in animals. This study imputes a function for TRPC3 at the onset of GSIS. These insights strengthen one’s knowledge of insulin secretion physiology and set forth the TRPC3 channel as an appealing candidate for drug development in the treatment of diabetes. 2023-06-08T13:11:58Z 2023-06-08T13:11:58Z 2023 Artículo Rached, G. et al. TRPC3 regulates islet beta-cell insulin secretion [en línea]. Advanced Science. 2023, 10 (6). doi: 10.1002/advs.202204846. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/16494 2198-3844 (online) https://repositorio.uca.edu.ar/handle/123456789/16494 10.1002/advs.202204846 36642838 eng Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Advanced Science. Vol.10 ; No.6, 2023 |
| institution |
Universidad Católica Argentina |
| institution_str |
I-33 |
| repository_str |
R-139 |
| collection |
Repositorio Institucional de la Universidad Católica Argentina (UCA) |
| language |
Inglés |
| topic |
TRPC3 INSULINA GLUCOSA CANALES CATIONICOS PROTEINA RECEPTORA TRANSITORIA 3 CELULAS BETA |
| spellingShingle |
TRPC3 INSULINA GLUCOSA CANALES CATIONICOS PROTEINA RECEPTORA TRANSITORIA 3 CELULAS BETA Rached, Gaëlle Saliba, Youakim Maddah, Dina Hajal, Joelle Smayra, Viviane Bakhos, Jules Joel Groschner, Klaus Birnbaumer, Lutz Farès, Nassim TRPC3 regulates islet beta-cell insulin secretion |
| topic_facet |
TRPC3 INSULINA GLUCOSA CANALES CATIONICOS PROTEINA RECEPTORA TRANSITORIA 3 CELULAS BETA |
| description |
Abstract: Insulin release is tightly controlled by glucose-stimulated calcium (GSCa)
through hitherto equivocal pathways. This study investigates TRPC3, a
non-selective cation channel, as a critical regulator of insulin secretion and
glucose control. TRPC3’s involvement in glucose-stimulated insulin secretion
(GSIS) is studied in human and animal islets. TRPC3-dependent in vivo
insulin secretion is investigated using pharmacological tools and Trpc3−/−
mice. TRPC3’s involvement in islet glucose uptake and GSCa is explored
using fluorescent glucose analogue 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)
amino]-2-deoxy-D-glucose and calcium imaging. TRPC3 modulation by a
small-molecule activator, GSK1702934A, is evaluated in type 2 diabetic mice.
TRPC3 is functionally expressed in human and mouse islet beta cells.
TRPC3-controlled insulin secretion is KATP-independent and primarily
mediated by diacylglycerol channel regulation of the cytosolic calcium
oscillations following glucose stimulation. Conversely, glucose uptake in islets
is independent of TRPC3. TRPC3 pharmacologic inhibition and knockout in
mice lead to defective insulin secretion and glucose intolerance. Subsequently,
TRPC3 activation through targeted small-molecule enhances insulin secretion
and alleviates diabetes hallmarks in animals. This study imputes a function
for TRPC3 at the onset of GSIS. These insights strengthen one’s knowledge of
insulin secretion physiology and set forth the TRPC3 channel as an appealing
candidate for drug development in the treatment of diabetes. |
| format |
Artículo |
| author |
Rached, Gaëlle Saliba, Youakim Maddah, Dina Hajal, Joelle Smayra, Viviane Bakhos, Jules Joel Groschner, Klaus Birnbaumer, Lutz Farès, Nassim |
| author_facet |
Rached, Gaëlle Saliba, Youakim Maddah, Dina Hajal, Joelle Smayra, Viviane Bakhos, Jules Joel Groschner, Klaus Birnbaumer, Lutz Farès, Nassim |
| author_sort |
Rached, Gaëlle |
| title |
TRPC3 regulates islet beta-cell insulin secretion |
| title_short |
TRPC3 regulates islet beta-cell insulin secretion |
| title_full |
TRPC3 regulates islet beta-cell insulin secretion |
| title_fullStr |
TRPC3 regulates islet beta-cell insulin secretion |
| title_full_unstemmed |
TRPC3 regulates islet beta-cell insulin secretion |
| title_sort |
trpc3 regulates islet beta-cell insulin secretion |
| publisher |
Wiley |
| publishDate |
2023 |
| url |
https://repositorio.uca.edu.ar/handle/123456789/16494 |
| work_keys_str_mv |
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1807949179737079808 |