Ciliary neurotrophic factor stimulates muscle glucose uptake by a PI3-kinase-dependent pathway that is impaired with obesity.

Diabetes
G R SteinbergSebastian Beck Jørgensen

Abstract

Ciliary neurotrophic factor (CNTF) reverses muscle insulin resistance by increasing fatty acid oxidation through gp130-LIF receptor signaling to the AMP-activated protein kinase (AMPK). CNTF also increases Akt signaling in neurons and adipocytes. Because both Akt and AMPK regulate glucose uptake, we investigated muscle glucose uptake in response to CNTF signaling in lean and obese mice. Mice were injected intraperitoneally with saline or CNTF, and blood glucose was monitored. The effects of CNTF on skeletal muscle glucose uptake and AMPK/Akt signaling were investigated in incubated soleus and extensor digitorum longus (EDL) muscles from muscle-specific AMPKalpha2 kinase-dead, gp130(DeltaSTAT), and lean and obese ob/ob and high-fat-fed mice. The effect of C2-ceramide on glucose uptake and gp130 signaling was also examined. CNTF reduced blood glucose and increased glucose uptake in isolated muscles in a time- and dose-dependent manner with maximal effects after 30 min with 100 ng/ml. CNTF increased Akt-S473 phosphorylation in soleus and EDL; however, AMPK-T172 phosphorylation was only increased in soleus. Incubation of muscles from AMPK kinase dead (KD) and wild-type littermates with the PI3-kinase inhibitor LY-294002 demonstrate...Continue Reading

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Citations

Sep 22, 2010·The Journal of Biological Chemistry·Gregory R SteinbergBruce E Kemp
Sep 27, 2012·American Journal of Therapeutics·Joselyn RojasValmore Bermúdez
Feb 28, 2009·Acta Physiologica·N L Dzamko, G R Steinberg
May 19, 2011·Biochemistry. Biokhimii︠a︡·M N Kostjukova, N N Tupitsyn
Jan 29, 2016·Cytokine·Sarah PasquinJean-François Gauchat
Sep 3, 2009·Molecular and Cellular Endocrinology·Sandra GalicGregory R Steinberg
Oct 1, 2009·Diabetes/metabolism Research and Reviews
Jan 2, 2013·Journal of Molecular and Cellular Cardiology·Mohamed AsrihChristophe Montessuit
Jan 24, 2015·International Journal of Obesity : Journal of the International Association for the Study of Obesity·L YuanG Yang
May 14, 2009·American Journal of Physiology. Endocrinology and Metabolism·Sebastian Beck JørgensenGregory R Steinberg
Aug 5, 2017·American Journal of Physiology. Cell Physiology·Song GaoJames A Carson
Nov 30, 2019·Frontiers in Endocrinology·Jessica PeruginiAntonio Giordano
May 15, 2015·American Journal of Physiology. Endocrinology and Metabolism·Nina BrandtSebastian B Jørgensen
Mar 10, 2015·American Journal of Physiology. Gastrointestinal and Liver Physiology·Hae-Ki MinArun J Sanyal

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BETA
immunoprecipitation

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ImageQuant TL

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