Intestinal aminooligopeptidase in diabetic BioBreed rat: altered posttranslational processing and trafficking

The structure of aminooligopeptidase (AOP), an intestinal brush-border dige stive hydrolase, is abnormal in human diabetes and in the congenitally diab etic BioBreed Wistar (BBd) rat. Its assembly in the BBd rat was examined. A fter normal initial synthesis and assembly of immature AOP precursor (AOP(i )) with high-mannose N-linked chains in the endoplasmic reticulum (ER), pro cessing of N-linked glycans in Golgi yielded a smaller than normal mature A OP precursor (AOP(m)) with persistence of some high-mannose N-linked chains . Deglycosylation analyses suggested that the mass difference could be attr ibuted to a lower mass of N-linked with unaltered O-linked glycans in AOP(m ) of the diabetic rat. Intrajejunal pulse-chase experiments revealed that t he conversion of AOP(i) to AOP(m) occurred at 30 min of chase in normal rat s but at 60-90 min in diabetic rats, reflecting delay in ER-to-Golgi transp ort or a slower processing of high-mannose chains. Once maximal transport t o Golgi was achieved, the residence time in Golgi was shortened in diabetes . This altered processing of the precursor accounted for the altered struct ure of AOP in diabetes.