Hyperaminoacidemia induces pancreatic α cell proliferation via synergism between the mTORC1 and CaSR-Gq signaling pathways

Yulong Gong, Bingyuan Yang, Dingdong Zhang, Yue Zhang, Zihan Tang, Liu Yang, Katie C. Coate, Linlin Yin, Brittney A. Covington, Ravi S. Patel, Walter A. Siv, Katelyn Sellick, Matthew Shou, Wenhan Chang, E. Danielle Dean, Alvin C. Powers and Wenbiao Chen ()
Additional contact information
Yulong Gong: Vanderbilt University
Bingyuan Yang: Vanderbilt University
Dingdong Zhang: Vanderbilt University
Yue Zhang: Vanderbilt University
Zihan Tang: Vanderbilt University
Liu Yang: Vanderbilt University
Katie C. Coate: Vanderbilt University Medical Center
Linlin Yin: Vanderbilt University
Brittney A. Covington: Vanderbilt University
Ravi S. Patel: Vanderbilt University
Walter A. Siv: Vanderbilt University Medical Center
Katelyn Sellick: Vanderbilt University Medical Center
Matthew Shou: Vanderbilt University Medical Center
Wenhan Chang: University of California San Francisco and San Francisco VA Medical Center
E. Danielle Dean: Vanderbilt University
Alvin C. Powers: Vanderbilt University
Wenbiao Chen: Vanderbilt University

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-35705-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35705-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-35705-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().