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Adenovirus36 E4orf1 and Lithium inhibit GSK3, but only E4orf1 increases glucose uptake in fat cells
Author(s) -
Dhurandhar Nikhil V,
Park SooHo,
Jeon HyunJung,
Dubuisson Olga,
Hegde Vijay,
Krishnapuram Rashmi,
Na HaNa,
Nam JaeHwan
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.630.18
Subject(s) - gsk 3 , glucose uptake , glycogen synthase , gsk3b , protein kinase b , chemistry , endocrinology , medicine , lithium (medication) , snf3 , glucose transporter , phosphorylation , biochemistry , biology , insulin
Inhibition of Glycogen synthase kinase (GSK)3 has been attempted as a therapeutic measure for diabetes, Alzheimer's disease, bipolarity, and some forms of cancers. The inhibition of GSK3 by some agents promotes cellular glucose uptake. We reported that Ad36, –a human adenovirus, increases cellular glucose uptake via its E4orf1 protein. Ad36 inhibits GSK3 by activating AKT2, a target of phosphatidyl inositol 3‐kinase activation. Here, we compared the ability of E4orf1, and Lithium (LI) ‐a widely used GSK3 inhibitor, to inhibit GSK3, and increase glucose uptake, in 3T3‐L1 cells. The, expression of E4orf1 in 3T3‐L1 preadipocytes, activated AKT, inhibited GSK3 as indicated by the phosphorylation of GSK‐3α/βserine 21 and serine 9 respectively, and increased glucose uptake, compared with cells expressing the null vector. LI (LiCl, 20mM), also inhibited GSK3, but did not activate AKT, and in fact, decreased, glucose uptake in 3T3‐L1 preadipocytes. Similarly, in 3T3‐L1 adipocytes, E4orf1 enhanced glucose uptake, whereas, LI reduced it. Thus, even if the potential of LI to inhibit GSK3 may be useful in many conditions, LI appears ineffective to improve glucose uptake in fat cells. Whereas, E4orf1 offers a template to increase glucose uptake and may be evaluated for its therapeutic application for additional diseases that would benefit from GSK3 inhibition. Funding: Vital Health Interventions.