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Aegeline From Aegle Marmelos Stimulates Glucose Transport via Akt and Rac1 Signaling, and Contributes to a Cytoskeletal Rearrangement Through PI3K/Rac1

Aegeline From Aegle Marmelos Stimulates Glucose Transport via Akt and Rac1 Signaling, and Contributes to a Cytoskeletal Rearrangement Through PI3K/Rac1

Sudeep Gautam, Nayab Ishrat, Rohit Singh, Tadigoppula Narender, Arvind K Srivastava

Eur J Pharmacol. 2015 Sep 5;762:419-29.

PMID: 26102565

Abstract:

Aegeline is an alkaloidal-amide, isolated from the leaves of Aegle marmelos and have shown antihyperglycemic as well as antidyslipidemic activities in the validated animal models of type 2 diabetes mellitus. Here we delineate, aegeline enhanced GLUT4 translocation mediated 2-deoxy-glucose uptake in both time and concentration-dependent manner. 2-deoxy-glucose uptake was completely stymied by the transport inhibitors (wortmannin and genistein) in C2C12 myotubes. Pharmacological inhibition of Akt (also known as protein kinase B) and Ras-related C3 botulinum toxin substrate 1 (Rac1) suggest that both Akt and Rac1 operate aegeline-stimulated glucose transport via distinct parallel pathways. Moreover, aegeline activates p21 protein-activated kinase 1 (PAK1) and cofilin (an actin polymerization regulator). Rac1 inhibitor (Rac1 inhib II) and PAK1 inhibitor (IPA-3) completely blocked aegeline-induced phosphorylation of cofilin and p21 protein-activated kinase 1 (PAK1). In summary, these findings suggest that aegeline stimulates the glucose transport through Akt and Rac1 dependent distinct parallel pathways and have cytoskeletal roles via stimulation of the PI3-kinase-Rac1-PAK1-cofilin pathway in the skeletal muscle cells. Therefore, multiple targets of aegeline in the improvement of insulin sensitivity of the skeletal muscle cells may be suggested.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP456122	Aegeline		456-12-2	Price

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