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. 2023 Jul 7;15(7):1514. doi: 10.3390/v15071514

Figure 1.

Figure 1

GLUT4 translocation through AD-36 and metformin. Insulin binding to its receptor activates a signaling pathway first regulated by a series of phosphorylation and then by adaptor protein recruitment; this pathway ultimately ends in GLUT4 translocation to cell membrane, which promotes glucose internalization. Abbreviations: IRS = insulin receptor substrate; PI3K = phosphoinositide 3-kinase; PIP2 = phosphatidylinositol-4,5-bisphosphate; PIP3 = phosphatidylinositol-3,4,5-trisphosphate; PDK1 = phosphoinositide-dependent kinase 1; Akt = protein kinase B; mTORC2 = mammalian target of rapamycin 2; AD-36 = adenovirus-36; e4orf1 = E4 open reading frame 1; PPAR-g = peroxisome proliferator-activated receptor-γ; GSV = GLUT4 storage vesicles; GLUT4 = glucotransporter 4; APS = adapter protein containing PH and SH2 domains; CAP = CBL-associated protein; c-CBL = cellular homolog of the transforming v-Cbl oncogene; CRK = adaptor protein CRK; C3G = guanine exchange factor C3G; TC10 = small GTP-binding protein TC10; Exo70 = subunit 70 of exocist complex. Modified from Sayem, 2018 [22]. (A). In vitro models have shown AD-36 interacts with insulin pathway and induces GLUT4 translocation through PPARγ upregulation, which favors GLUT4 transcription. Moreover, AD-36 E4orf1 gene also activates PI3K signaling and leads to GLUT4 translocation to cell membrane. (B). On the other hand, metformin intervenes in insulin signaling pathway in a different mechanism; it regulates CAP and c-CBL proteins and increases GLUT4 translocation from GSV to membrane.