Insulin deficiency induces abnormal increase in intestinal disaccharidase activities and expression under diabetic states, evidences from in vivo and in vitro study

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Abstract

Graphical abstract

Insulin regulates disaccharidase activities and expression partly via the MAPK-dependent pathway and its deficiency induces abnormal increase in intestinal disaccharidase activities and expression under diabetic states.

Structural and functional alterations in the gastrointestinal tract of diabetic patients are often accompanied by increase in absorption of intestinal glucose and activities of brush-border disaccharidases. The purpose of this study was to investigate the role of insulin in regulating intestinal disaccharidases using in vivo and in vitro experiments. Streptozotocin-induced diabetic rats and normal rats received protamine zinc insulin (10 IU/kg) subcutaneously twice daily for 5 weeks. Disaccharidase activities and sucrase–isomaltase (SI) complex protein and mRNA expression in intestinal regions were assessed. In addition, Caco-2 cells were cultured in medium containing glucose, insulin or insulin plus some pharmacological inhibitors for 7 days, disaccharidase activities, sucrase–isomaltase (SI) complex and Cdx2 mRNA levels were measured. The animal experiments showed that diabetes increased intestinal disaccharidase activities, accompanied by high mRNA and protein expression of SI complex. Insulin treatment reversed the increases induced by diabetes. The cellular results showed that insulin suppressed disaccharidase activities and down-regulated SI complex and Cdx2 mRNA expression in a concentration-dependent manner. The inhibitor of MAPK signal pathway PD-98059 blocked the suppression of disaccharidase activities and expression of SI complex and Cdx2 mRNA induced by insulin. In conclusion, insulin deficiency induces abnormal increase in intestinal disaccharidase activities and expression under diabetic states. Insulin plays an essential role in regulation disaccharidase activities and expression, at least in part, via the MAPK-dependent pathway.

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