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.

Joo-Hui Han,Sang-Gil Lee,Chang-Seon Myung,In-Su Kim,Hwa-Young Son,Sang-Hyuk Jung,Cedric Moro

doi:10.1371/journal.pone.0095268

Joo-Hui Han, Sang-Gil Lee + Show 5 more

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https://doi.org/10.1371/journal.pone.0095268

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Journal: PloS one	Publication Date: Apr 18, 2014
Citations: 78	License type: CC BY 4.0

Affiliation: Chungnam National University

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.

Highlights

Diabetes mellitus is the most common metabolic disease and its increased prevalence has raised attention as a worldwide public health problem
GPR41 Expression To confirm the presence of GPR41, mRNA and protein expression levels of GPR41 were measured in 3T3-L1 preadipocytes, differentiated 3T3-L1 adipocytes, C2C12 myoblasts, and differentiated C2C12 myotubes
(2) both propionic acid and valeric acid increased insulinstimulated glucose uptake in 3T3-L1 adipocytes and basal glucose uptake in C2C12 myotubes via, at least in part, GPR41. This is the first report that propionic acid and valeric acid ameliorate insulin sensitivity via, at least in part, GPR41 by stimulating insulin-induced glucose uptake into adipocytes and basal glucose uptake into skeletal muscle cells

Summary

Introduction

Diabetes mellitus is the most common metabolic disease and its increased prevalence has raised attention as a worldwide public health problem. Type 2 diabetes does not involve a lack of insulin secretion but rather is characterized by insulin resistance, a state in which insulin has a reduced ability to mediate glucose homeostasis in its major target tissues, such as skeletal muscle, adipose tissue, and liver [2]. The first step by which insulin increases energy storage or utilization involves the regulated transport of glucose into the cell [6]. Glucose transport in insulin-sensitive tissues (skeletal muscle and adipose tissue) is a control point for the regulation of blood glucose levels, and a possible target for the derangement of glucose homeostasis in certain disease states, such as type 2 diabetes [7]

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