Feeding-induced hepatokines and crosstalk with multi-organ: A novel therapeutic target for Type 2 diabetes

Front Endocrinol (Lausanne). 2023 Mar 3:14:1094458. doi: 10.3389/fendo.2023.1094458. eCollection 2023.

Abstract

Hyperglycemia, which can be caused by either an insulin deficit and/or insulin resistance, is the main symptom of Type 2 diabetes, a significant endocrine metabolic illness. Conventional medications, including insulin and oral antidiabetic medicines, can alleviate the signs of diabetes but cannot restore insulin release in a physiologically normal amount. The liver detects and reacts to shifts in the nutritional condition that occur under a wide variety of metabolic situations, making it an essential organ for maintaining energy homeostasis. It also performs a crucial function in glucolipid metabolism through the secretion of hepatokines. Emerging research shows that feeding induces hepatokines release, which regulates glucose and lipid metabolism. Notably, these feeding-induced hepatokines act on multiple organs to regulate glucolipotoxicity and thus influence the development of T2DM. In this review, we focus on describing how feeding-induced cross-talk between hepatokines, including Adropin, Manf, Leap2 and Pcsk9, and metabolic organs (e.g.brain, heart, pancreas, and adipose tissue) affects metabolic disorders, thus revealing a novel approach for both controlling and managing of Type 2 diabetes as a promising medication.

Keywords: feeding-induced hepatokines; glucolipid metabolism; insulin resistance; multi-organ; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / metabolism
  • Humans
  • Insulin / metabolism
  • Liver / metabolism

Substances

  • Insulin

Grants and funding

This work was supported by National Natural Science Foundation of China [grant numbers 82070873, 82000813] and the Project of Hunan Provincial Clinical Research Center for Diabetes [grant number 2019SK4005].