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Intestinal aminooligopeptidase in diabetic BioBreed rat: altered posttranslational processing and trafficking
S M Najjar1, J P Broyart, L T Hampp
1Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. snajjar@mco.edu
American Journal of Physiology. Gastrointestinal and Liver Physiology
|December 21, 2000
Summary
Diabetes alters aminooligopeptidase (AOP) assembly in rats. Impaired N-linked glycan processing and delayed ER-to-Golgi transport in diabetic rats lead to abnormal AOP structure, impacting intestinal digestion.
Area of Science:
- Biochemistry
- Cell Biology
- Endocrinology
Background:
- Aminooligopeptidase (AOP) is an intestinal brush-border enzyme crucial for digestion.
- Structural abnormalities in AOP are observed in human and rat diabetes models.
Purpose of the Study:
- To investigate the assembly process of AOP in the diabetic BioBreed Wistar (BB(d)) rat.
- To understand how diabetes affects AOP precursor processing and transport.
Main Methods:
- Pulse-chase experiments in vivo (intrajejunal).
- Analysis of N-linked and O-linked glycans.
- Deglycosylation studies.
- Examination of AOP precursor processing in endoplasmic reticulum (ER) and Golgi.
Main Results:
- Diabetic rats showed normal initial synthesis of immature AOP (AOP(i)) but produced a smaller mature AOP (AOP(m)) with persistent high-mannose N-linked glycans.
- Deglycosylation indicated reduced N-linked glycan mass in AOP(m) from diabetic rats.
- ER-to-Golgi transport of AOP(i) was delayed (60-90 min vs. 30 min in controls), and Golgi residence time was shortened in diabetic rats.
Conclusions:
- Altered N-linked glycan processing and delayed transport contribute to the abnormal AOP structure in diabetes.
- These processing defects in the diabetic rat model offer insights into AOP dysfunction in diabetes.
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