INS and Other metabolic disease: From the biological point of view, it is interesting that the PN approach models, for the first time, the experimentally well-known insulin-stimulated degradation of IR [47,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90] which plays a fundamental role in the insulin resistance and metabolic disorders [55,57,59,60].