INTESTINAL MUCOSAL FUNCTION IN DIABETES

糖尿病的肠粘膜功能

• 批准号: 3225165
• 负责人: WARD A OLSEN
• 金额: $ 8.07万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-06-15 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3225165
• 关键词: active transport; alpha glucosidase; beta fructofuranosidase; binding proteins; brush border membrane; cell membrane; diabetes mellitus; gastrointestinal absorption /transport; gastrointestinal nutrient absorption; gel electrophoresis; genetic transcription; genetic translation; glucose tolerance test; glycoproteins; human subject; hydrolase; hypoglycemic agents; ileum; intestinal mucosa; intestinal villi; jejunum; laboratory rat; membrane lipids; membrane permeability; membrane proteins; messenger RNA; nutrition related tag; organ culture; pancreas enzyme; pancreatitis; protein metabolism; radiotracer; tritium

Uncontrolled diabetes mellitus in the rat results in multiple alterations in the function of the brush border membrane of the enterocyte including the stimulation of active transport mechanisms and increases in a variety of membrane-bound hydrolases. Elucidation of the mechanisms involved may provide important insight into the patho-physiology of the human disease as well as into the nature of the regulation of brush border proteins. Our long term objective is to elucidate these mechanisms. Our specific aims are to answer the following questions: (1) is the increased rate of biosynthesis of sucrase- isomaltase in diabetic animals the result of transcriptional, translational, or posttranslational changes; (2) are the changes specific or is there altered regulation of all brush border hydrolases; (3) what are the mediators of altered regulation; (4) are alterations in hydrolases in other situations related to the diabetic changes. To answer these questions we will study the effects of diabetes and other conditions where hydrolase activity is altered on synthesis and intracellular processing of precursors of selected brush border hydrolases. This will be done by pulse/chase experiments followed by immune precipitation and SDS-polyacrylamide gel electrophoresis and fluorography and by immunoelectron microscopy. Effects on mRNA levels will be sought in cell free translational experiments, and the effects of several possible mediators on biosynthetic processes in organ- cultured intestine determined. Finally, since intracellular processing of these proteins is incompletely understood, we will, in the course of these experiments, define more clearly this processing in normal rat intestine and, in the case of several hydrolases, human intestine.

不受控制的糖尿病大鼠可导致多发性