INS and obesity due to melanocortin 4 receptor deficiency: The pro-inflammatory cytokines, such as TNF-α and IL-6, produced by adipose tissue and obesity might act as the initiating factors in inflammatory response (the “driver” role), which might then activate various signal transduction cascades in the cells of insulin responsive tissues, leading to inhibition of insulin signaling, insulin resistance, and T2D [25–29].