Inhibition of the post‐translational processing of microvillar hydrolases is associated with a specific decreased expression of sucrase‐isomaltase and an increased turnover of glucose in Caco‐2 cells treated with monensin

Abstract

The biosynthesis and post‐translational processing of sucrase‐isomaltase and dipeptidylpeptidase IV were studied by L‐[³⁵S]methionine labeling, immunoisolation with monoclonal antibodies and SDS‐PAGE in post‐confluent Caco‐2 cells treated with monensin (10 μM, 48 h). In addition to its classical effect on the post‐translational processing of both hydrolases, i.e. an inhibition of the conversion of the high‐mannose to the complex glycosylated form of the enzymes, monensin was found to have two other effects: a marked decrease of sucrase‐isomaltase expression, but not of dipeptidylpeptidase IV; an increased turnover of glucose, as substantiated by increased rates of glucose consumption and lactic acid production and a decreased glycogen content. Whether these two effects are related to the particular differentiation and metabolic status of Caco‐2 cells is discussed, as well as a possible role for the drug‐induced modifications of glucose turnover on the decreased expression of sucrase‐isomaltase.