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Transcriptomic responses and molecular mechanisms of glucagon-regulated glucose metabolism in Japanese flounder (Paralichthys olivaceus)

Year: 2026

Type: article

Abstract: Glucagon is a key hormone regulating gluconeogenesis and glucose homeostasis in mammals, yet its regulatory mechanisms in glucose metabolism in carnivorous fish remain incompletely understood. To systematically investigate glucagon-mediated glucose metabolism in Japanese flounder ( Paralichthys olivaceus ), liver samples were collected before glucagon injection (0 h) and at 1 h and 6 h post-injection for transcriptome sequencing (RNA-seq). Transcriptome analysis identified numerous differentially expressed genes involved in glucose and energy metabolism. In total, 507, 1458, and 709 differentially expressed genes were detected in the comparisons of 0 h vs 1 h, 1 h vs 6 h, and 0 h vs 6 h, respectively. KEGG enrichment analysis showed that glucagon activated pathways related to glucagon signaling, insulin resistance, FoxO signaling, and energy metabolism, including AMPK and PPAR pathways, suggesting that glucagon rapidly stimulates gluconeogenesis. At 6 h post-injection, genes involved in glycolysis and glucose transport were upregulated, whereas key gluconeogenic genes were downregulated, indicating attenuation of glucagon-induced metabolic responses. Further analysis showed that glucagon suppressed the insulin-mediated PI3K/AKT signaling pathway. Among the candidate genes, SOCS3 and TRIB3 were upregulated and may serve as key regulators linking glucagon and insulin signaling. Functional experiments further showed that knockdown of TRIB3 reduced glucose levels in hepatocyte culture medium and increased the expression of insulin signaling-related genes. Overall, glucagon regulates glucose metabolism in Japanese flounder by promoting gluconeogenesis while suppressing insulin signaling, providing transcriptomic insights into endocrine regulation in carnivorous fish.

Source: Frontiers in Physiology

DOI: 10.3389/fphys.2026.1825972

Authors: Ting Zhang, Hongquan Wang, Tiaoyi Xiao, Mengxi Yang, Wenbing Zhang

Institutions: Hunan Agricultural University, Ministry of Agriculture and Rural Affairs, Ocean University of China

Language: English

Topic: Metabolism, Diabetes, and Cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,801

Funder: National Natural Science Foundation of China