title: The effects of propionate and valerate on insulin responsiveness for glucose uptake in 3T3-L1 adipocytes and C2C12 myotubes via G protein-coupled receptor 41.
abstract: Since insulin resistance can lead to hyperglycemia, improving glucose uptake into target tissues is critical for regulating blood glucose levels. Among the free fatty acid receptor (FFAR) family of G protein-coupled receptors, GPR41 is known to be the Gαi/o-coupled receptor for short-chain fatty acids (SCFAs) such as propionic acid (C3) and valeric acid (C5). This study aimed to investigate the role of GPR41 in modulating basal and insulin-stimulated glucose uptake in insulin-sensitive cells including adipocytes and skeletal muscle cells. Expression of GPR41 mRNA and protein was increased with maximal expression at differentiation day 8 for 3T3-L1 adipocytes and day 6 for C2C12 myotubes. GPR41 protein was also expressed in adipose tissues and skeletal muscle. After analyzing dose-response relationship, 300 µM propionic acid or 500 µM valeric acid for 30 min incubation was used for the measurement of glucose uptake. Both propionic acid and valeric acid increased insulin-stimulated glucose uptake in 3T3-L1 adipocyte, which did not occur in cells transfected with siRNA for GPR41 (siGPR41). In C2C12 myotubes, these SCFAs increased basal glucose uptake, but did not potentiate insulin-stimulated glucose uptake, and siGPR41 treatment reduced valerate-stimulated basal glucose uptake. Therefore, these findings indicate that GPR41 plays a role in insulin responsiveness enhanced by both propionic and valeric acids on glucose uptake in 3T3-L1 adipocytes and C2C12 myotubes, and in valerate-induced increase in basal glucose uptake in C2C12 myotubes.
authors.affiliation: Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon, Republic of Korea.
authors.forename: Joo-Hui
authors.initials: JH
authors.lastname: Han
authors.affiliation: Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon, Republic of Korea.
authors.forename: In-Su
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon, Republic of Korea.
authors.forename: Sang-Hyuk
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon, Republic of Korea.
authors.forename: Sang-Gil
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Department of Veterinary Pathology, Chungnam National University College of Veterinary Medicine, Daejeon, Republic of Korea.
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Son
authors.affiliation: Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon, Republic of Korea; Institute of Drug Research & Development, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Chang-Seon
authors.initials: CS
authors.lastname: Myung
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D010421:Pentanoic Acids / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D007328:Insulin; D010421:Pentanoic Acids; D011422:Propionates; D043562:Receptors, G-Protein-Coupled; C038780:n-pentanoic acid; D005947:Glucose; C029658:propionic acid
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