PUBLICATION
Hyperaminoacidemia induces pancreatic α cell proliferation via synergism between the mTORC1 and CaSR-Gq signaling pathways
- Authors
- Gong, Y., Yang, B., Zhang, D., Zhang, Y., Tang, Z., Yang, L., Coate, K.C., Yin, L., Covington, B.A., Patel, R.S., Siv, W.A., Sellick, K., Shou, M., Chang, W., Danielle Dean, E., Powers, A.C., Chen, W.
- ID
- ZDB-PUB-230117-12
- Date
- 2023
- Source
- Nature communications 14: 235235 (Journal)
- Registered Authors
- Chen, Wenbiao
- Keywords
- none
- MeSH Terms
-
- Animals
- Calcium/metabolism
- Cell Proliferation
- Female
- Glucagon
- Glucagon-Secreting Cells*/metabolism
- Male
- Mechanistic Target of Rapamycin Complex 1*/metabolism
- Mice
- Receptors, Calcium-Sensing*/metabolism
- Signal Transduction*
- Zebrafish/metabolism
- PubMed
- 36646689 Full text @ Nat. Commun.
Citation
Gong, Y., Yang, B., Zhang, D., Zhang, Y., Tang, Z., Yang, L., Coate, K.C., Yin, L., Covington, B.A., Patel, R.S., Siv, W.A., Sellick, K., Shou, M., Chang, W., Danielle Dean, E., Powers, A.C., Chen, W. (2023) Hyperaminoacidemia induces pancreatic α cell proliferation via synergism between the mTORC1 and CaSR-Gq signaling pathways. Nature communications. 14:235235.
Abstract
Glucagon has emerged as a key regulator of extracellular amino acid (AA) homeostasis. Insufficient glucagon signaling results in hyperaminoacidemia, which drives adaptive proliferation of glucagon-producing α cells. Aside from mammalian target of rapamycin complex 1 (mTORC1), the role of other AA sensors in α cell proliferation has not been described. Here, using both genders of mouse islets and glucagon receptor (gcgr)-deficient zebrafish (Danio rerio), we show α cell proliferation requires activation of the extracellular signal-regulated protein kinase (ERK1/2) by the AA-sensitive calcium sensing receptor (CaSR). Inactivation of CaSR dampened α cell proliferation, which was rescued by re-expression of CaSR or activation of Gq, but not Gi, signaling in α cells. CaSR was also unexpectedly necessary for mTORC1 activation in α cells. Furthermore, coactivation of Gq and mTORC1 induced α cell proliferation independent of hyperaminoacidemia. These results reveal another AA-sensitive mediator and identify pathways necessary and sufficient for hyperaminoacidemia-induced α cell proliferation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
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