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  3. ErbB3 is required for hyperaminoacidemia-induced pancreatic α cell hyperplasia

ErbB3 is required for hyperaminoacidemia-induced pancreatic α cell hyperplasia

  • J Biol Chem. 2024 Jun 27;300(8):107499. doi: 10.1016/j.jbc.2024.107499.
Qi Kang 1,  Jianxin Jia 1,  E Danielle Dean 2,  Hang Yuan 1,  Chunhua Dai 2,  Zhehui Li 1,  Fuquan Jiang 1,  Xiao-Kun Zhang 1,  Alvin C Powers 3,  Wenbiao Chen 4,  Mingyu Li 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences and School of Life Sciences, Xiamen University, Xiamen, China; Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China.
  • 2 Departments of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • 3 Departments of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; VA Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
  • 4 Departments of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. Electronic address: wenbiao.chen@vanderbilt.edu.
  • 5 School of Pharmaceutical Sciences and School of Life Sciences, Xiamen University, Xiamen, China; Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China; State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, China. Electronic address: limingyu@xmu.edu.cn.
PMID: 38944125 DOI: 10.1016/j.jbc.2024.107499
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 mechanistic target of rapamycin complex 1, another ErbB3 downstream effector signal transducer and activator of transcription 3 also plays a role in α cell hyperplasia. Mechanistically, ErbB3 may partner with ErbB2 to stimulate cyclin D2 and suppress p27 via mechanistic target of rapamycin complex 1 and signal transducer and activator of transcription 3. 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.

Keywords

diabetes; glucagon receptor; hyperaminoacidemia; α cell; α cell hyperplasia.

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