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Improved Glucose Intolerance through a Distinct Mouse Olfactory Receptor 23‐Induced Signaling Pathway Mediating Glucose Uptake in Myotubes and Adipocytes
Author(s) -
Kang Wesuk,
Zhang Kelun,
Tong Tao,
Park Taesun
Publication year - 2020
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201901329
Subject(s) - medicine , endocrinology , glucose homeostasis , glucose uptake , myogenesis , adipose tissue , insulin receptor , signal transduction , biology , downregulation and upregulation , insulin , chemistry , microbiology and biotechnology , insulin resistance , biochemistry , myocyte , gene
Scope It is aimed to determine the role of mouse olfactory receptor 23 (MOR23) in regulation of glucose uptake in myotubes and adipocytes and investigate whether administration of a possible MOR23 ligand, α‐cedrene, attenuates the high fat diet (HFD)‐induced glucose intolerance by enhancing the OR‐mediated signaling pathway in mice. Methods and Results MOR23 is genetically inactivated by specific small interfering RNA in C2C12 myotubes and 3T3‐L1 adipocytes and stimulated with α‐cedrene under both basal and insulin‐stimulated conditions. In addition, Male C57BL/6N mice are fed a normal diet, HFD, or HFD supplemented with 0.2% α‐cedrene. In C2C12 myotubes and 3T3‐L1 adipocytes, genetic inactivation of MOR23 significantly decrease glucose uptake and MOR23 downstream signaling under both basal and insulin‐stimulated conditions. On the other hand, α‐cedrene‐mediated MOR23 stimulation results in increased glucose uptake and upregulation of MOR23 signaling molecules, absent in MOR23‐depleted myotubes and adipocytes. Moreover, in mice, α‐cedrene administration ameliorates HFD‐induced glucose intolerance. Activation of MOR23 signaling cascade is also confirmed in basal and insulin stimulated skeletal muscles and adipose tissues of α‐cedrene‐treated mice. Conclusions These findings suggest that MOR23 is a novel factor for the regulation of glucose uptake and whole‐body glucose homeostasis and has therapeutic potential for diabetes treatment.