HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Yue, P. Articles by Tsao, P. S. PubMed PubMed Citation Articles by Yue, P. Articles by Tsao, P. S.

RESEARCH ARTICLE

Apelin is necessary for the maintenance of insulin sensitivity

¹Stanford University

Submitted 16 June 2009 ; revised 19 October 2009 ; accepted in final form 19 October 2009

BACKGROUND: The recently discovered peptide apelin is known to be involved in the maintenance of insulin sensitivity. However, questions persist regarding its precise role in the chronic setting. METHODS: Fasting glucose, insulin, and adiponectin levels were determined on mice with generalized deficiency of apelin (APKO). Additionally, insulin (ITT) and glucose tolerance tests (GTT) were performed. To assess the impact of exogenously delivered apelin on insulin sensitivity, osmotic pumps containing pyroglutamated apelin-13 or saline were implanted in APKO mice for 4 weeks. Following the infusion, ITT/GTTs were repeated and the animals sacrificed. Soleus muscles were harvested, homogenized in lysis buffer, and insulin-induced Akt phosphorylation determined by Western blotting. Apelin-13 infusion and ITT/GTTs were also performed in obese diabetic db/db mice. To probe the underlying mechanism for apelin's effects, apelin-13 was also delivered to cultured C2C12 myotubes. 2-[³H]-deoxyglucose uptake and Akt phosphorylation were assessed in the presence of various inhibitors. RESULTS: APKO mice had diminished insulin sensitivity, were hyperinsulinemic, and had decreased adiponectin levels. Soleus lysates had decreased insulin-induced Akt phosphorylation. Administration of apelin to APKO and db/db mice resulted in improved insulin sensitivity. In C2C12 myotubes, apelin increased glucose uptake and Akt phosphorylation. These events were fully abrogated by pertussis toxin, Compound C, and siRNA knockdown of AMPK1, but only partially diminished by LY294002, and not at all by LNAME. CONCLUSIONS: Apelin is necessary for the maintenance of insulin sensitivity in vivo. Apelin's effects on glucose uptake and Akt phosphorylation are in part mediated by a Gi and AMPK-dependent pathway.

apelin; insulin resistance; signal transduction