Metformin Improves Insulin Signaling in Obese Rats via Reduced IKK Action in a Fiber-Type Specific Manner

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Ethan J. Anderson (Creator)

Benjamin T. Bikman (Creator)

Ronald N. Cortright (Creator)

G. Lynis Dohm (Creator)

Daniel A. Kane (Creator)

P. Darrell Neufer (Creator)

Jesse W. Price (Creator)

Tracey L. Woodlief (Creator)

Donghai Zheng (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Metformin is a widely used insulin-sensitizing drug, though its mechanisms are not fully understood. Metformin has been shown to activate AMPK in skeletal muscle; however, its effects on the inhibitor of ?B kinaseß (IKKß) in this same tissue are unknown. The aim of this study was to (1) determine the ability of metformin to attenuate IKKß action, (2) determine whether changes in AMPK activity are associated with changes in IKKß action in skeletal muscle, and (3) examine whether changes in AMPK and IKKß function are consistent with improved insulin signaling. Lean and obese male Zuckers received either vehicle or metformin by oral gavage daily for four weeks (four groups of eight). Proteins were measured in white gastrocnemius (WG), red gastrocnemius (RG), and soleus. AMPK phosphorylation increased (P < .05) in WG in both lean (57%) and obese (106%), and this was supported by an increase in phospho-ACC in WG. Further, metformin increased I?Ba levels in both WG (150%) and RG (67%) of obese rats, indicative of reduced IKKß activity (P < .05), and was associated with reduced IRS1-pSer307 (30%) in the WG of obese rats (P < .02). From these data we conclude that metformin treatment appears to exert an inhibitory influence on skeletal muscle IKKß activity, as evidenced by elevated I?Ba levels and reduced IRS1-Ser307 phosphorylation in a fiber-type specific manner.

Additional Information

Publication

Other

Journal of Obesity; 2010: p. 1-8

Language: English

Date: 2010

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