INS and diabetes mellitus: Our results revealed that similar alterations can be found in a variety of pre-diabetic animals (hProC(A7)Y-CpepGFP and LepRdb/db), namely heterogeneous impairment in proinsulin maturation (Figure 1) and ER distention [30], implying that ER-crowding may function as a common pathophysiological mechanism in the development of pre-diabetes irrespective to the pathogenetic cause of ER-crowding.