IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle.
Altered energy balance and insulin resistance are important characteristics of aging. Skeletal muscle is a major site of glucose disposal, and the role of aging-associated inflammation in skeletal muscle insulin resistance remains unclear. To investigate, we examined glucose metabolism in 18-mo-old transgenic mice with muscle-specific overexpression of IL-10 (MIL10) and in wild-type mice during hyperinsulinemic-euglycemic clamping. Despite similar fat mass and energy balance, MIL10mice were protected from aging-associated insulin resistance with significant increases in glucose infusion rates, whole-body glucose turnover, and skeletal muscle glucose uptake (∼60%; P < 0.05), as compared to age-matched WT mice. This protective effect was associated with decreased muscle inflammation, but no changes in adipose tissue inflammation in aging MIL10mice. These results demonstrate the importance of skeletal muscle inflammation in aging-mediated insulin resistance, and our findings further implicate a potential therapeutic role of anti-inflammatory cytokine in the treatment of aging-mediated insulin resistance.-Dagdeviren, S., Jung, D. Y., Friedline, R. H., Noh, H. L., Kim, J. H., Patel, P. R., Tsitsilianos, N., Inashima, K., Tran, D. A., Hu, X., Loubato, M. M., Craige, S. M., Kwon, J. Y., Lee, K. W., Kim, J. K. IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle.
Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Sezin
S
Dagdeviren
Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Dae Young
DY
Jung
Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Randall H
RH
Friedline
Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Hye Lim
HL
Noh
Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|Wellness Emergence Center, Advanced Institutes of Convergence Technology, Seoul National University, Suwon, South Korea.
Jong Hun
JH
Kim
Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Payal R
PR
Patel
Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Nicholas
N
Tsitsilianos
Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Kunikazu
K
Inashima
Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Duy A
DA
Tran
Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Xiaodi
X
Hu
Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Marilia M
MM
Loubato
Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Siobhan M
SM
Craige
Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|Wellness Emergence Center, Advanced Institutes of Convergence Technology, Seoul National University, Suwon, South Korea.
Jung Yeon
JY
Kwon
Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea; and.|Wellness Emergence Center, Advanced Institutes of Convergence Technology, Seoul National University, Suwon, South Korea.
Ki Won
KW
Lee
Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; jason.kim@umassmed.edu.|Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea; and.|Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Jason K
JK
Kim
D000375:Aging / Q000502:physiology*; D000818:Animals; D052283:Creatine Kinase, MM Form; D004734:Energy Metabolism; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism*
D016753:Interleukin-10; D052283:Creatine Kinase, MM Form
 cytokines; aging; glucose metabolism; interleukins; type 2 diabetes