INS and type 2 diabetes mellitus: The above data are in agreement with our previous studies indicating that a progressive decline in insulin sensitivity in UCP3+/− heterozygous mice and UCP3−/− mice [11] and with clinical observations reporting that (i) a 50% reduction of UCP3 protein in human SkM is correlated with the incidence of T2DM [39], (ii) in humans, the UCP3 protein levels are reduced in the pre-diabetic state of impaired glucose tolerance [40,41], (iii) heterozygous mutations in the UCP3 gene (V56M, A111V, V192I, and Q252X) in children was associated with dyslipidemia and lower insulin sensitivity [42].