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 glucose 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 insulin to reduce to normal the elevated blood glucose levels has also been assessed. The maximum capacity (Vmax) for SGLT1-mediated glucose uptake by BBM vesicles was unaffected by diabetes or insulin treatment of diabetic rats. In contrast, Vmax for BLM glucose uptake was increased by 206% in diabetes, a response that could not be reversed by treatment with insulin. Western blotting of BBM for SGLT1 protein revealed 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 changes in glycaemic or insulin status. Diabetes hyperpolarised the BBM, implying an increased driving force for Na(+)-sugar co-transport but insulin treatment only partially reversed this enhanced potential difference. Benzamil (2 microns), an epithelial Na+ channel blocker, hyperpolarised the BBM of control but not diabetic enterocytes, implying that a reduced Na+ permeability was responsible for the diabetic hyperpolarisation. It was concluded that in early diabetes, before the onset of hyperphagia, a greater driving force for Na(+)-dependent BBM sugar transport together with increased GLUT2 activity at the BLM promotes sugar movement across the enterocyte. Possible triggers for the transport responses are discussed.
Sharp
P A
PA
Department of Physiology, Royal Free Hospital School of Medicine, London, UK.
Boyer
S
S
Srai
S K
SK
Baldwin
S A
SA
Debnam
E S
ES
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000648:ultrastructure; D007425:Intracellular Membranes / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose