Abstract
BackgroundEvidence demonstrates that exogenously administered nitric oxide (NO) can induce insulin resistance in skeletal muscle. We have investigated the modulatory effects of two NO donors, S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and S-nitrosoglutathione (GSNO) on the early events in insulin signaling in rat skeletal myocytes.ResultsSkeletal muscle cells from 6–8 week old Sprague-Dawley rats were treated with SNAP or GSNO (25 ng/ml) in the presence or absence of glucose (25 mM) and insulin (100 nM). Cellular insulin receptor-β levels and tyrosine phosphorylation in IRS-1 were significantly reduced, while serine phosphorylation in IRS-1 was significantly increased in these cells, when compared to the insulin-stimulated control. Reversal to near normal levels was achieved using the NO scavenger, 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO).ConclusionThese data suggest that NO is a potent modulator of insulin-mediated signal transduction and may play a significant role in the pathogenesis of type 2 diabetes mellitus.
Highlights
Evidence demonstrates that exogenously administered nitric oxide (NO) can induce insulin resistance in skeletal muscle
Effect of Nitric oxide (NO) released from SNAP and GSNO on insulin receptor-β (IR-β) expression Figure 3 illustrates the inhibitory effects of NO released from SNAP and GSNO on IR-β expression in isolated rat skeletal myocytes
There was a slight increase in the expression of IR-β in cells treated with the NO donor and insulin when compared to those treated with the NO donor alone (p > 0.05); in the case of GSNO, the increase approached significance
Summary
Evidence demonstrates that exogenously administered nitric oxide (NO) can induce insulin resistance in skeletal muscle. Nitric oxide (NO) is an important bioactive molecule that regulates a variety of normal physiological functions and is involved in the mediation of several pathologic processes [1,2]. It is a short-lived free radical gas and endogenous signalling molecule produced by the intracellular enzyme NO synthase [2]. We have established that exogenous NO (from NO-releasing drugs) inhibited in vivo insulin binding to its receptor on erythrocytes and mononuclear leukocytes [3], and in vitro glucose uptake in skeletal muscle cells [4] and adipocytes (unpublished results). Phosphorylation of IRS-1 on multiple tyrosine residues creates an active signalling complex by (page number not for citation purposes)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
