EARLY DIABETES-INDUCED CHANGES IN RAT JEJUNAL GLUCOSE-TRANSPORT AND THE RESPONSE TO INSULIN

The effects of 1 day of streptozotocin-induced diabetes in rats on glu cose transport across the brush border membrane (BBM) and basolateral membrane (BLM) prepared from jejunal enterocytes has been studied. The effects on glucose transport of treatment of diabetic animals with in sulin to reduce to normal the elevated blood glucose levels has also b een assessed. The maximum capacity (V-max) for SGLT1-mediated glucose uptake by BBM vesicles was unaffected by diabetes or insulin treatment of diabetic rats. In contrast, V-max for BLM glucose uptake was incre ased by 206% in diabetes, a response that could not be reversed by tre atment with insulin. Western blotting of BBM for SGLT1 protein reveale d a single band with a molecular weight of 73 kDa and the intensity of this band was unaffected by diabetes. However, an increased level of GLUT2 was noted in diabetic BLM and this was not a consequence of chan ges in glycaemic or insulin status. Diabetes hyperpolarised the BBM, i mplying an increased driving force for Na+-sugar co-transport but insu lin treatment only partially reversed this enhanced potential differen ce. Benzamil (2 mu M), an epithelial Na channel blocker, hyperpolarise d the BBM of control but not diabetic enterocytes, implying that a red uced Na+ permeability was responsible for the diabetic hyperpolarisati on. It was concluded that in early diabetes, before the onset of hyper phagia, a greater driving force for Na+-dependent BBM sugar transport together with increased GLUT2 activity at the BLM promotes sugar movem ent across the enterocyte. Possible triggers for the transport respons es are discussed.