Induction of glucose uptake in skeletal muscle by central leptin is mediated by muscle β2-adrenergic receptor but not by AMPK

Leptin increases glucose uptake and fatty acid oxidation (FAO) in red-type skeletal muscle. However, the mechanism remains unknown. We have investigated the role of β 2 -adrenergic receptor (AR), the major β-AR isoform in skeletal muscle, and AMPK in leptin-induced muscle glucose uptake of mice. Lep...

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Bibliographic Details
Published in:Scientific reports 2017-11, Vol.7 (1), p.1-11, Article 15141
Main Authors: Shiuchi, Tetsuya, Toda, Chitoku, Okamoto, Shiki, Coutinho, Eulalia A., Saito, Kumiko, Miura, Shinji, Ezaki, Osamu, Minokoshi, Yasuhiko
Format: Article
Language:English
Subjects:
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Adrenergic receptors
AKT protein
Glucose
Humanities and Social Sciences
Hypothalamus (ventromedial)
Insulin
Leptin
multidisciplinary
Musculoskeletal system
Norepinephrine
Oxidation
Phosphorylation
Rodents
Science
Science (multidisciplinary)
Skeletal muscle
Sympathetic nerves
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Summary:Leptin increases glucose uptake and fatty acid oxidation (FAO) in red-type skeletal muscle. However, the mechanism remains unknown. We have investigated the role of β 2 -adrenergic receptor (AR), the major β-AR isoform in skeletal muscle, and AMPK in leptin-induced muscle glucose uptake of mice. Leptin injection into the ventromedial hypothalamus (VMH) increased 2-deoxy-D-glucose (2DG) uptake in red-type skeletal muscle in wild-type (WT) mice accompanied with increased phosphorylation of the insulin receptor (IR) and Akt as well as of norepinephrine (NE) turnover in the muscle. Leptin-induced 2DG uptake was not observed in β-AR-deficient (β-less) mice despite that AMPK phosphorylation was increased in the muscle. Forced expression of β 2 -AR in the unilateral hind limb of β-less mice restored leptin-induced glucose uptake and enhancement of insulin signalling in red-type skeletal muscle. Leptin increased 2DG uptake and enhanced insulin signalling in red-type skeletal muscle of mice expressing a dominant negative form of AMPK (DN-AMPK) in skeletal muscle. Thus, leptin increases glucose uptake and enhances insulin signalling in red-type skeletal muscle via activation of sympathetic nerves and β 2 -AR in muscle and in a manner independent of muscle AMPK.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-15548-6