A Feeding-induced Myokine Modulates Glucose Homeostasis

Overview

Journal Nat Metab

Publisher Springer Nature

Specialty Endocrinology

Date 2025 Jan 2

PMID 39747483

Authors

Xiaoliu Shi

Xiao Hu

Xinlei Fang

Liangjie Jia

Fangchao Wei

Ying Peng

Menghao Liu

Aibo Gao

Ke Zhao

Fengyi Chen

Xiaoli Hu

Jie Hong

Guang Ning

Yongfeng Song

Jiqiu Wang

Yiguo Wang

Affiliations

Soon will be listed here.

Abstract

Maintaining blood glucose homeostasis during fasting and feeding is crucial for the prevention of dysregulation that can lead to either hypo- or hyperglycaemia. Here we identified feimin, encoded by a gene with a previously unknown function (B230219D22Rik in mice, C5orf24 in humans), as a key modulator of glucose homeostasis. Feimin is secreted from skeletal muscle during feeding and binds to its receptor, receptor protein tyrosine kinase Mer (MERTK), promoting glucose uptake and inhibiting glucose production by activation of AKT. Administration of feimin and insulin synergistically improves blood glucose homeostasis in both normal and diabetic mice. Notably, a specific single nucleotide polymorphism (rs7604639, G>A) within the MERTK gene, causing an amino acid substitution (R466K) within the feimin-MERTK binding region, leads to reduced association with feimin and elevated postprandial blood glucose and insulin levels in humans. Our findings underscore a role of the feimin-MERTK signalling axis in glucose homeostasis, providing valuable insights into potential therapeutic avenues for diabetes.

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