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. 2021 Aug 24;12:717544. doi: 10.3389/fendo.2021.717544

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Copyright © 2021 Lu, Huang, Huang, Feng, Clark and Chen

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The counter-regulatory effects of LEAP-2 and ghrelin. (A) LEAP-2 blocks whereas ghrelin activates the GHS-R1a on target cells (e.g., somatotroph, NPY/AgRP neurons, and islet β cells) to exert biological functions on regulating GH secretion, appetite and GSIS, respectively. Ghrelin inhibits hepatic LEAP-2 mRNA expression, while LEAP-2’s effect on ghrelin expression is still unknown. (B) The LEAP-2/ghrelin molar ratio. This ratio changes accordingly to energy status and correlates positively with BMI and some metabolic parameters. ↑, increase; ↓, decrease; -, inhibit; +, activate; ?, unknown; GH, growth hormone; GSIS, glucose-stimulated insulin secretion; NPY/AgRP, neuropeptide Y/agouti-related protein; BMI, body mass index; HOMA-IR, homeostatic model assessment for insulin resistance.