THE REGULATION OF GLUT5 AND GLUT2 ACTIVITY IN THE ADAPTATION OF INTESTINAL BRUSH-BORDER FRUCTOSE TRANSPORT IN DIABETES

The adaptation of D-fructose transport in rat jejunum to experimental diabetes has been studied. In vivo and in vitro perfusions of intact j ejunum with D-fructose revealed the appearance of a phloretin-sensitiv e transporter in the brush-border membrane of streptozotocin-diabetic rats which was not detectable in normal rats. The nature of the transp orters involved was investigated by Western blotting and by D-fructose transport studies using highly purified brush-border and basolateral membrane vesicles. GLUTS, the major transporter in the brush-border me mbrane of normal rats, was not inhibited by D-glucose or phloretin. In contrast, GLUT2, the major transporter in the basolateral membrane of normal rats, was strongly inhibited by both D-glucose and phloretin. In brush-border membrane vesicles from diabetic rats, GLUTS levels wer e significantly enhanced; moreover the presence of GLUT2 was readily d etectable and increased markedly as diabetes progressed. The differenc es in stereospecificity between GLUT2 and GLUTS were used to show that both transporters contributed to the overall enhancement of D-fructos e transport measured in brush-border membrane vesicles and in vitro is olated loops from diabetic rats. However, overall D-fructose uptake in vivo was diminished. The underlying mechanisms and functional consequ ences are discussed.