[HTML][HTML] Inefficient translocation of preproinsulin contributes to pancreatic β cell failure and late-onset diabetes

H Guo, Y Xiong, P Witkowski, J Cui, L Wang… - Journal of Biological …, 2014 - ASBMB
Among the defects in the early events of insulin biosynthesis, proinsulin misfolding and
endoplasmic reticulum (ER) stress have drawn increasing attention as causes of β cell
failure. However, no studies have yet addressed potential defects at the cytosolic entry point
of preproinsulin into the secretory pathway. Here, we provide the first evidence that
inefficient translocation of preproinsulin (caused by loss of a positive charge in the n region
of its signal sequence) contributes to β cell failure and diabetes. Specifically, we find that …