PUBLICATION
ErbB3 is required for hyperaminoacidemia-induced pancreatic α cell hyperplasia
- Authors
- Kang, Q., Jia, J., Dean, E.D., Yuan, H., Dai, C., Li, Z., Jiang, F., Zhang, X.K., Powers, A.C., Chen, W., Li, M.
- ID
- ZDB-PUB-240630-5
- Date
- 2024
- Source
- The Journal of biological chemistry 300(8): 107499 (Journal)
- Registered Authors
- Chen, Wenbiao, Li, Mingyu
- Keywords
- diabetes, glucagon receptor, hyperaminoacidemia, α cell, α cell hyperplasia
- MeSH Terms
-
- Amino Acids/metabolism
- Animals
- Cell Line
- Cell Proliferation
- Cyclin D2*/genetics
- Cyclin D2*/metabolism
- Glucagon-Secreting Cells*/metabolism
- Glucagon-Secreting Cells*/pathology
- Humans
- Hyperplasia*/metabolism
- Hyperplasia*/pathology
- Mechanistic Target of Rapamycin Complex 1*/metabolism
- Mice
- Receptor, ErbB-2/genetics
- Receptor, ErbB-2/metabolism
- Receptor, ErbB-3*/genetics
- Receptor, ErbB-3*/metabolism
- STAT3 Transcription Factor/genetics
- STAT3 Transcription Factor/metabolism
- Signal Transduction
- Zebrafish*
- PubMed
- 38944125 Full text @ J. Biol. Chem.
Citation
Kang, Q., Jia, J., Dean, E.D., Yuan, H., Dai, C., Li, Z., Jiang, F., Zhang, X.K., Powers, A.C., Chen, W., Li, M. (2024) ErbB3 is required for hyperaminoacidemia-induced pancreatic α cell hyperplasia. The Journal of biological chemistry. 300(8):107499.
Abstract
Blood amino acid levels are maintained in a narrow physiological range. The pancreatic α cells have emerged as the primary aminoacidemia regulator through glucagon secretion to promote hepatic amino acid catabolism. Interruption of glucagon signaling disrupts the liver - α cells axis leading to hyperaminoacidemia, which triggers a compensatory rise in glucagon secretion and α cell hyperplasia. The mechanisms of hyperaminoacidemia-induced α cell hyperplasia remain incompletely understood. Using a mouse α cell line and in vivo studies in zebrafish and mice, we found that hyperaminoacidemia-induced α cell hyperplasia requires ErbB3 signaling. In addition to mTORC1, another ErbB3 downstream effector STAT3 also plays a role in α cell hyperplasia. Mechanistically, ErbB3 may partner with ErbB2 to stimulate cyclin D2 and suppress p27 via mTORC1 and STAT3. Our study identifies ErbB3 as a new regulator for hyperaminoacidemia-induced α cell proliferation and a critical component of the liver-α cells axis that regulates aminoacidemia.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping