INS and obesity due to melanocortin 4 receptor deficiency: Hence, in face of resistance to insulin in the glycemic context, insulin-driven Erk/RSK may transduce a variety of mTORC1-mediated disease aspects of T2D (e.g., beta cell failure, obesity, NAFLD, dyslipidemia, hypertension, diabetes macro- and micro-vascular disease) as outlined below (Fig. 5).