Preliminary Evidence for Adipocytokine Signals in Skeletal Muscle Glucose Uptake.

Akihiro Kudoh,Tsuyoshi Watanabe,Hiroaki Satoh,Michio Shimabukuro,Hiroyuki Hirai

doi:10.3389/fendo.2018.00295

Abstract

The cross talk between the adipose tissue and insulin target tissues is a key mechanism for obesity-associated insulin resistance. However, the precise role of the interaction between the skeletal muscle and adipose tissue for insulin signaling and glucose uptake is questionable. L6 myocytes were co-cultured with or without 3T3-L1 adipocytes (~5 × 103 cells/cm2) up to 24 h. Glucose uptake was evaluated by 2-[3H] deoxyglucose uptake assay. Levels of mRNA expression of Glut1 and Glut4 and mitochondrial enzymes were analyzed by quantitative real-time reverse transcription polymerase chain reaction. Levels of Glut1 and Glut4 protein and phosphorylation of Akt (Ser473 and Thr308) were analyzed by immunoblotting. Study 1: co-culture with 3T3-L1 adipocytes increased glucose uptake in dose- and time-dependent manner in L6 myocytes under insulin-untreated conditions. When co-cultured with 3T3-L1 cells, reactive oxygen species production and levels of Glut1 mRNA and protein were increased in L6 cells, while these changes were abrogated and the glucose uptake partially inhibited by antioxidant treatment. Study 2: co-culture with 3T3-L1 adipocytes suppressed insulin-stimulated glucose uptake in L6 myocytes. Insulin-induced Akt phosphorylation at Ser473 decreased, which was proportional to 3T3-L1 density. Antioxidant treatment partially reversed this effect. Interactions between skeletal muscle and adipose tissues are important for glucose uptake under insulin-untreated or -treated condition through oxygen stress mechanism.

Highlights

Obesity and the associated insulin resistance are thought to be the major cause of the global epidemic of type 2 diabetes
Study 1: Insulin-Independent Glucose Uptake in L6 Myocytes Co-Cultured With 3T3-L1 Adipocytes
Total RNA extracted from L6 cells co-cultured for 18 h with 5 × 103 3T3-L1 cells (Figures 2A,C) was used for mRNA quantification of Glut1 and glucose transporter 4 (Glut4)

Summary

Introduction

Obesity and the associated insulin resistance are thought to be the major cause of the global epidemic of type 2 diabetes. Overflow of lipids from the expanded adipose cells in obese individuals is considered as the key mechanism for the obesity-associated insulin resistance [1,2,3]. Other mechanisms related to the cross talk between the adipose tissue and insulin target tissues have been identified. Skeletal Muscle and Adipose Tissue Interactions called adipocytokines or adipokines. These molecules signal key organs to maintain metabolic homeostasis [4, 5]. Several studies have shown the alteration in the secretory profile of adipocytokines in obese subjects and some of these factors are known to display important roles in inducing insulin resistance [6]

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