Drosophila melanogaster as a Model for Diabetes Type 2 Progression

Figure 1

The insulin signaling pathway. The binding of insulin to its receptor initiates a phosphorylation cascade that results in the regulation of metabolism through several effectors. Names for the vertebrate counterparts of the pathway appear below their Drosophila names. CAT-1: cationic amino acid transporter-1; Imp-L2: ecdysone-inducible gene L2; IGFBPs: insulin-like growth factor binding proteins; ASL: acid-labile subunit; SDR: secreted decoy of InR; dILPs 1–7: insulin-like ligands 1–7; IGFs: insulin-like growth factors; InR: insulin receptor; IRS/chico: insulin receptor substrate; PI3K: phosphatidylinositol 3-kinase (two subunits: Pi3K92E is the catalytic subunit, and Pi3K21B is the regulatory subunit); PIP2: phosphatidylinositol 4,5-bisphosphate; PIP3: phosphatidylinositol 3,4,5-trisphosphate; PTEN: phosphatase and tensin homolog; dPDK1: 3-phosphoinositide dependent protein kinase-1; GSK3β: glycogen synthase kinase 3 beta; Tsc1-2: tuberous sclerosis proteins 1 and 2; Rheb: Ras homolog enriched in brain; TOR-C1: target of rapamycin complex 1 (the TOR-C1 complex consists primarily of TOR, regulatory associated protein of TOR (raptor), and lethal with Sec-13 protein 8 (LST8)); TOR-C2: target of rapamycin complex 2 (the TOR-C2 complex consists primarily of TOR, rapamycin-insensitive companion of TOR (Rictor), and stress-activated protein kinase-interacting protein 1 (Sin1)); Myc: Myc protein; SREBP: sterol regulatory element-binding protein; S6K: ribosomal protein S6 kinase beta-1; 4E-BP: eukaryotic translation initiation factor 4E-binding protein 1; FoxO: Forkhead box O transcription factor. Dashed lines indicate an indirect interaction; arrows and bar-headed lines indicate activation and inhibition, respectively.