Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

Figure 3

Negative regulation exerted by insulin-sensitizing on the molecular mechanism feeding insulin resistance. Role of AMPK as a metformin and myo-Ins molecular target. AMPK activation induces COX2 inhibition, p53 expression, and mTORC1 silencing through TSC2 and Raptor phosphorylation. The regulating activity of AMPK in processes of tumour induction and progression suggest that metformin may be proposed as an anticancer agent. TNFα: Tumour Necrosis Factor α; IL-6: interleukin 6; IR: insulin receptor; PKC: protein kinase C; JNK: c-Jun N-terminal Kinase; NFκB: nuclear factor κB; IRS-1: insulin receptor substrate 1; PI(3,4,5)P3: phosphatidylinositol 3,4,5-trisphosphate; Akt: protein kinase B; GLUT4: glucose transporter type 4; TSC1: tuberous sclerosis 1; TSC2 tuberous sclerosis 2; AMPK 5′: adenosine monophosphate-activated protein kinase; AMP: adenosine monophosphate; LKB1: liver kinase B1; CaMKKβ: calcium/calmodulin-dependent protein kinase β; Pras40: Proline-Rich Akt/PKB Substrate 40 kDa; RHEB: Ras Homolog Enriched in Brain; mTOR: mammalian target of rapamycin; Raptor: regulatory-associated protein of mTOR; mTORC1: mammalian target of rapamycin complex 1; 6SK1: 6S Kinase 1; 4EBP1: Eukaryotic Translation Initiation Factor 4E-Binding Protein 1; ACC: Acetyl-CoA Carboxylase; p53: Tumour Protein 53; COX2: cyclooxygenase 2.