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• W298859248 abstract "Background : It was previously observed that nicotine induced insulin resistance in mice. Nicotine activates nicotinic-acetylcholine-receptors (nAChR). Inhibition of nAChR or nitric oxide synthase (NOS) prevented nicotine- induced hyperglycemia. Functional nAChR pentamers are composed of combinations of [alpha]1-10, [beta]1-4, [gamma], [delta], and [epsilon] subunits. It has been reported that specific activation of [alpha]7nAchR prevents diabetes. Therefore, determination of the subunit expression profile in liver and muscle and analysis of the effects of nicotine on insulin signaling would help elucidate the pathway of nicotine action in liver and muscle. Hypothesis : Prolonged exposure to nicotine may inhibit insulin-stimulated PI-3 -kinase/Akt signaling in liver and muscle tissues which may not express [alpha]7nAChR subunit for protection. Methods : (i) Analysis of mRNA expressions of the nAChR subunits in liver and muscle by qRT- PCR. (ii) Analysis of the effects of nicotine on insulin-stimulated phosphorylation of Akt and ERK-1/2 in hepatocytes, muscle and chromaffin cells by immunoblotting. Results : The predominant nAChR subunits are, [beta]4[alpha]3[alpha]7[alpha]10 in adrenal glands, [beta]4[alpha]10[alpha]3 in liver and [beta]4[alpha]10[alpha]1[beta]1 in muscle. Liver and muscle do not express [alpha]7nAChR. Nicotine treatment (16 hours) inhibited insulin-stimulated Akt phosphorylation in hepatocytes and muscle cells but not in PC-12 cells. This inhibition was reversed by pretreatment with nAChR and NOS-inhibitors. Nicotine treatment stimulated ERK phosphorylation and enhanced insulin effects in hepatocytes but not in muscle cells. Conclusions : The lack of [alpha]7 and differential expression of nAChR subunits in liver and muscle may be responsible for the inhibition of insulin-stimulated Akt signaling by nicotine leading to insulin resistance" @default.
• W298859248 created "2016-06-24" @default.
• W298859248 creator A5047374228 @default.
• W298859248 date "2012-01-01" @default.
• W298859248 modified "2023-09-27" @default.
• W298859248 title "Expression of nicotinic acetylcholine receptor (nAChR) in peripheral tissues and the effects of nicotine on insulin signaling" @default.
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