title: Insulin deficiency induces abnormal increase in intestinal disaccharidase activities and expression under diabetic states, evidences from in vivo and in vitro study.
abstract: 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.
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China. liulee@cpu.edu.cn
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Yun-Li
authors.initials: YL
authors.lastname: Yu
authors.forename: Can
authors.initials: C
authors.lastname: Liu
authors.forename: Xin-Ting
authors.initials: XT
authors.lastname: Wang
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D004186:Disaccharidases / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000627:therapeutic use*; D007422:Intestines / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D007336:Insulin, Isophane; D004186:Disaccharidases