Insulin and exercise increase skeletal muscle glucose uptake, and insulin-mediated glucose uptake is defective in type 2 diabetes patients. To identify genes that regulate glucose uptake in skeletal muscle, we conducted a systematic review to identify genes whose experimental gain- or loss-of-function increases or decreases skeletal muscle glucose uptake in mice. We found that the manipulation of 47 genes increases glucose uptake as measured by accumulation of 2-deoxyglucose in skeletal muscle. The effect size ranged from +10 to +650% and results from the manipulation of the following genes: Slc2a1, Aifm1, Itga2, Ucp3, Cd36, Stk11, Prkcq, Tp53, Trib3, Pik3c3, Igfbp1, Mtor, Igf1r, Cat, Hbegf, Slc2a4, Hk2, Foxc2, Sphk1, Dgat2, Sirt6, Ptpn1, Mapk8, Tbc1d1, Abhd5, Lipa, Txnip, Nos2, Abcc6, Kcna3, Ptpn6, Slc2a12, Timp3, Camk4, Hmga1, Ddah1, Id2, Gnas, Pik3r1, Fasn, Mstn, Cept1, Rxrg, Apob, Il10, Dgat1, Prkag3. Furthermore, we found 40 genes whose gain or loss-of-function decreased glucose uptake in muscle ranging from -15% to -70%. These genes are: Hdac3, Cav3, Irs1, Vegfa, Nob1, Ppargc1a, Agt, Gfpt1, Ptprf, Lpl, Enpp1, Il6, Cpt1c, Sirt1, Tbc1d1, Itgb1, Mmp9, Igf1r, Ankrd26, Insr, Nos3, Igf1r, Inppl1, Stxbp3, Pea15, Ceacam1, Rrad, Tbc1d4, Dgat2, Lnpep, Pparg, Lipe, Dgat1, Rictor, Prkab2, Rab28, Igfbp1, Ptpn11, Igfbp3, Ski. In summary, glucose uptake is a polygenic trait that is influenced by more than 80 genes in mice.
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