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A review of epidermal growth factor receptor ligands in glucose homeostasis
Ka-Ying Chan1, Chu-Jun Deng1, Xi Chen1
1Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China.
Abstract:
The epidermal growth factor receptor (EGFR/ErbB1) is a critical regulator of cellular proliferation and differentiation. While its role in oncology is well-characterized, its contribution to glucose homeostasis has emerged as a significant area of metabolic research. This mini-review synthesizes current evidence regarding the seven EGFR ligands-EGF, TGFα, amphiregulin, HB-EGF, betacellulin, epiregulin, and epigen-in regulating beta cell mass, insulin secretion, hepatic gluconeogenesis, and peripheral insulin sensitivity. We critically evaluate the transition from mechanistic in vitro studies to preclinical rodent models, while acknowledging the current lack of human clinical validation. Furthermore, we discuss the metabolic paradox of EGFR tyrosine kinase inhibitors (TKIs) and the safety considerations regarding the mitogenic potential of these ligands. By highlighting emerging evidence and structural innovations such as chimeric ligands, this review provides a roadmap for future translational research in the EGFR/ErbB metabolic signaling axis.
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