Tiam-1, a GEF for Rac1, plays a critical role in metformin-mediated glucose uptake in C2C12 cells
- Authors
- You, Ga Young; Lee, Jung Ok; Kim, Ji Hae; Kim, Nami; Lee, Soo Kyung; Moon, Ji Wook; Jie, Sha; Lee, Hye Jeong; Kim, Su Jin; Park, Sun Hwa; Kim, Hyeon Soo
- Issue Date
- 12월-2013
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- AMPK; GEF; Glucose uptake; PAK1; Tiam-1
- Citation
- CELLULAR SIGNALLING, v.25, no.12, pp.2558 - 2565
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELLULAR SIGNALLING
- Volume
- 25
- Number
- 12
- Start Page
- 2558
- End Page
- 2565
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/101351
- DOI
- 10.1016/j.cellsig.2013.08.018
- ISSN
- 0898-6568
- Abstract
- Metformin is known to stimulate glucose uptake, but the mechanism for this action is not fully understood. In this study, AMPK activators (AICAR and metformin) increased the expression of T-lymphoma invasion and metastasis-inducing protein-1 (Tiam-1), a Rac1 specific guanine nucleotide exchange factor (GEF), mRNA and protein in skeletal muscle C2C12 cells. Metformin increases the serine-phosphorylation of Tiam-1 by AMPK and induces interaction between Tiam-1 and 14-3-3. Pharmacologic inhibition of AMPK blocks this interaction, indicating that 14-3-3 may be required for induction of Tiam-1 by AMPK. Metformin also increases the phosphorylation of p21-activated kinase 1 (PAK1), a direct downstream target of Rac1, dependent on AMPK. Tiam-1 is down-regulated at high glucose concentrations in cultured cells and in the db/db mouse model of hyperglycemia. Furthermore, Tiam-1 knock-down blocked metformin-induced increase in glucose uptake. These findings suggest that metformin promotes cellular glucose uptake in part through Tiam-1 induction. (C) 2013 Elsevier Inc. All rights reserved.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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