RGD Reference Report - Adrenaline increases glucose transport via a Rap1-p38MAPK pathway in rat vascular smooth muscle cells. - Rat Genome Database

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Adrenaline increases glucose transport via a Rap1-p38MAPK pathway in rat vascular smooth muscle cells.

Authors: Kanda, Y  Watanabe, Y 
Citation: Kanda Y and Watanabe Y, Br J Pharmacol. 2007 Jun;151(4):476-82. Epub 2007 Apr 23.
RGD ID: 10040970
Pubmed: (View Article at PubMed) PMID:17450172
DOI: Full-text: DOI:10.1038/sj.bjp.0707247

BACKGROUND AND PURPOSE: Adrenaline has been implicated in the pathogenesis of atherosclerosis. However, little is known regarding the role of adrenaline in glucose transport in VSMC. EXPERIMENTAL APPROACH: In this study, we examined the effects of adrenaline on glucose uptake in rat VSMC. We also examined the downstream signaling pathway from the beta-adrenoceptor to glucose uptake, using a pharmacological approach. To investigate the downstream action of adenylate cyclase, we studied the effects of GGTI-298, an inhibitor of geranylgeranylation of GTPases, including Rap1. To confirm the involvement of Rap1, we silenced Rap1 by siRNA. KEY RESULTS: Adrenaline induced glucose uptake in a dose-dependent manner. The adrenaline-induced glucose uptake was inhibited by L-propranolol, (a selective beta-adrenoceptor antagonist), but not by prazosin (a selective alpha(1)-adrenoceptor antagonist) or UK14304 (a selective alpha(2)-adrenoceptor antagonist), suggesting the involvement of beta-adrenoceptors in glucose transport. Long-term treatment with cholera toxin, which resulted in sequestration of G(s) proteins, prevented the adrenaline-induced glucose uptake. Forskolin, a direct activator of adenylate cyclase, was found to mimic the effects of adrenaline. Adrenaline-induced glucose uptake was inhibited by GGTI-298, not by H89 (a selective inhibitor of PKA). Silencing of Rap1 by siRNA attenuated the adrenaline-induced glucose uptake. Adrenaline-induced glucose uptake was inhibited by SB203580 (a selective inhibitor of p38MAPK) and adrenaline-induced p38MAPK activation was inhibited by GGTI-298 and siRNA against Rap1. CONCLUSIONS AND IMPLICATIONS: These findings suggest that adrenaline-induced glucose transport is mediated by beta-adrenoceptors, G(s), adenylate cyclase, Rap1, and p38MAPK in vascular smooth muscle cells.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Rap1a  (RAP1A, member of RAS oncogene family)


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