Macrophage migration inhibitory factor diminishes muscle glucose transport induced by insulin and AICAR in a muscle type-dependent manner.
Skeletal muscle is a primary organ that uses blood glucose. Insulin- and 5'AMP-activated protein kinase (AMPK)-regulated intracellular signaling pathways are known as major mechanisms that regulate muscle glucose transport. It has been reported that macrophage migration inhibitory factor (MIF) is secreted from adipose tissue and heart, and affects these two pathways. In this study, we examined whether MIF is a myokine that is secreted from skeletal muscles and affects muscle glucose transport induced by these two pathways. We found that MIF is expressed in several different types of skeletal muscle. Its secretion was also confirmed in C2C12 myotubes, a skeletal muscle cell line. Next, the extensor digitorum longus (EDL) and soleus muscles were isolated from mice and treated with recombinant MIF in an in vitro muscle incubation system. MIF itself did not have any effect on glucose transport in both types of muscles. However, glucose transport induced by a submaximal dose of insulin was diminished by co-incubation with MIF in the soleus muscle. MIF also diminished glucose transport induced by a maximal dose of 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR), an AMPK activator, in the EDL muscle. These results suggest that MIF is a negative regulator of insulin- and AICAR-induced glucose transport in skeletal muscle. Since MIF secretion from C2C12 myotubes to the culture medium decreased during contraction evoked by electrical stimulations, MIF may be involved in the mechanisms underlying exercise-induced sensitization of glucose transport in skeletal muscle.
Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
Shouta
S
Miyatake
Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
Yasuko
Y
Manabe
Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
Akiko
A
Inagaki
Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
Yasuro
Y
Furuichi
Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
Mayumi
M
Takagi
Department of Chemistry, Graduate School of Sciences and Engineering, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
Masato
M
Taoka
Department of Chemistry, Graduate School of Sciences and Engineering, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
Toshiaki
T
Isobe
Department of Anesthesiology, Kansai Medical University, Hirakata, Osaka 573-1191, Japan.
Kiichi
K
Hirota
Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan. Electronic address: fujiin@tmu.ac.jp.
Nobuharu L
NL
Fujii
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction
D007004:Hypoglycemic Agents; D007328:Insulin; D008263:Macrophage Migration-Inhibitory Factors; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C031143:AICA ribonucleotide; D005947:Glucose
Glucose transport; Macrophage migration inhibitory factor; Myokine; Skeletal muscle