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

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.

The Role of Chitinase-3-like Protein-1 (YKL40) in the Therapy of Cancer and Other Chronic-Inflammation-Related Diseases

“…Moreover, activated RhoA interacts with ROCK, promoting its activation. ROCK phosphorylates various substrates, including myosin light chain (MLC) and LIM kinase (LIMK), which results in cytoskeletal reorganization and the modulation of cell motility and adhesion [ 29 ]. This can contribute to immune cell recruitment and tissue inflammation.…”

Assessment of the Association between Genetic Polymorphisms in the <b><i>CHI3L1</i></b> Gene and Asthma Risk

“…CHI3L1 has high binding affinity for chitin and chitin oligosaccharides. It plays a role in numerous biological and pathological processes, including extracellular matrix formation, cell proliferation and differentiation, migration, chemotaxis, angiogenesis, inflammation, endothelial dysfunction, and tissue remodeling [ signaling pathways downstream of CHI3L1, including the mitogen-activated protein kinase pathway, the phosphoinositide 3-kinase/protein kinase B pathway, the c-Jun N-terminal kinase/caspase-3 pathway, and the cytokine signaling such as interleukin 1beta [28][29][30][31]. Over the recent decades, a number of studies have demonstrated that CHI3L1 is associated with asthma.…”

Myokines: Novel therapeutic targets for diabetic nephropathy

“…In addition to what we have summarized above, with the development of biotechnology, more and more myokines have been discovered, such as Apelin ( 116 ), Chitinase-3-like protein ( 117 ), Follistatin-like 1 ( 118 ), Dipeptidyl Peptidase IV ( 119 ), MG53 ( 120 ) and METRNL ( 121 ), which they also play a key role in maintaining the human homeostasis of the body. Further studies are needed to determine whether they are related to DN and, if so, how Table 1 .…”