Effect of chitinase-3-like protein 1 on glucose metabolism: In vitro skeletal muscle and human genetic association study

So Young Kwak, Il Hyeok Seo, In Hyeok Chung, Shin Ae Kim, Jung Ok Lee, Hye Jeong Lee, Sung Eun Kim, Jeong Ah Han, Min Ju Kang, Su Jin Kim, Soo Lim, Kyoung Min Kim, Ji Hyung Chung, Eunice Lim, Jong Ik Hwang, Hyeon Soo Kim, Min Jeong Shin

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

We investigated the effect of chitinase-3-like protein 1 (CHI3L1) on glucose metabolism and its underlying mechanisms in skeletal muscle cells, and evaluated whether the observed effects are relevant in humans. CHI3L1 was associated with increased glucose uptake in skeletal muscles in an AMP-activated protein kinase (AMPK)-dependent manner, and with increased intracellular calcium levels via PAR2. The improvement in glucose metabolism observed in an intraperitoneal glucose tolerance test on male C57BL/6J mice supported this association. Inhibition of the CaMKK was associated with suppression of CHI3L1-mediated glucose uptake. Additionally, CHI3L1 was found to influence glucose uptake through the PI3K/AKT pathway. Results suggested that CHI3L1 stimulated the phosphorylation of AS160 and p38 MAPK downstream of AMPK and AKT, and the resultant GLUT4 translocation. In primary myoblast cells, stimulation of AMPK and AKT was observed in response to CHI3L1, underscoring the biological relevance of CHI3L1. CHI3L1 levels were elevated in cells under conditions that mimic exercise in vitro and in exercised mice in vivo, indicating that CHI3L1 is secreted during muscle contraction. Finally, similar associations between CHI3L1 and metabolic parameters were observed in humans alongside genotype associations between CHI3L1 and diabetes at the population level. CHI3L1 may be a potential therapeutic target for the treatment of diabetes.

Original languageEnglish
Pages (from-to)13445-13460
Number of pages16
JournalFASEB Journal
Volume34
Issue number10
DOIs
Publication statusPublished - 2020 Oct 1

Bibliographical note

Funding Information:
This study was conducted with bioresources from National Biobank of Korea, the Centers for Disease Control and Prevention, Republic of Korea (KBP‐2018‐039). This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF‐2020R1A2C2005580) and by the Bio & Medical Technology Development Program of the NRF funded by the Ministry of Science & ICT (NRF‐2012M3A9C4048761). This study was also supported by a Korea University Grant.

Funding Information:
This study was conducted with bioresources from National Biobank of Korea, the Centers for Disease Control and Prevention, Republic of Korea (KBP-2018-039). This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2020R1A2C2005580) and by the Bio & Medical Technology Development Program of the NRF funded by the Ministry of Science & ICT (NRF-2012M3A9C4048761). This study was also supported by a Korea University Grant.

Publisher Copyright:
© 2020 Federation of American Societies for Experimental Biology

Keywords

  • AMPK
  • Chitinase-3-like protein 1
  • glucose metabolism
  • glucose uptake
  • myokine

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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