The effect of oral vanadate on intestinal sodium-dependent glucose transport and 6-phosphofructo-1-kinase (EC 2.7.1.11) activity was examined in male Sprague-Dawley rats following a 30-day period of non-treated streptozotocin-induced diabetes. Non-treated diabetic rats were hyperglycaemic and demonstrated increased intestinal sodium-dependent glucose transport and Na,K-ATPase activity compared with controls. These increases were associated with a significant decrease in the total activity and activity ratios (activity at 0.5 mmol/l fructose 6-phosphate at pH 7.0/activity at pH 8.0) of intestinal 6-phosphofructo-1-kinase and decreased levels of fructose 2,6-bisphosphate. Supplementation of drinking water with vanadate (0.5 mg/ml) resulted in a rapid decline in blood glucose levels to a slightly hyperglycaemic level. Jejunal glucose transport and Na,K-ATPase activity were normalized after 48 h of vanadate treatment. In contrast, ileal glucose transport was significantly reduced 12 h following beginning vanadate treatment even though Na,K-ATPase activity did not normalize until 36 h later. Km was significantly decreased in both jejunum and ileum by vanadate treatment indicating an increased affinity of the sodium-dependent intestinal glucose transporter for glucose. 6-phosphofructo-1-kinase total activity and susceptibility to ATP inhibition was completely restored after 12 h of vanadate treatment. This increase was associated with a rise in fructose 2,6-bisphosphate levels. Fasting rats for 12 h had no effect on glucose transport or 6-phosphofructo-1-kinase activity, indicating the anorectic effect of vanadate was not responsible for changes in either parameter. In contrast, cycloheximide prevented both the rise in 6-phosphofructo-1-kinase activity and the rise in fructose 2,6-bisphosphate levels, and the subsequent reduction in glucose transport, indicating a requirement for protein synthesis. The removal of vanadate resulted in an immediate return to pre-treatment blood glucose levels. In contrast, intestinal glucose transport and 6-phosphofructo-1-kinase activity remained at treatment levels up until 72 h, indicating that oral vanadate treatment can have prolonged beneficial effects on intestinal function. In conclusion, the treatment of streptozotocin-induced diabetic rats with oral vanadate results in an activation of 6-phosphofructo-1-kinase coupled with a normalization of intestinal sodium-dependent glucose transport. Vanadate may thus have a beneficial effect on intestinal function and may prove useful as oral adjunctive diabetic therapy.

The effect of insulin on intestinal sodium-dependent glucose transport and brush border membrane surface area was examined in male Sprague-Dawley rats following a 30-day period of nontreated streptozocin-induced diabetes. Nontreated diabetic rats were hyperglycemic and demonstrated increased jejunal and ileal Na-dependent glucose transport Jmax (maximal transport capacity) and Na-K ATPase activity compared with controls. Daily administration of insulin resulted in a steady decline in blood glucose levels over a period of 6 days. Jejunal Jmax was normalized after 2 days of insulin therapy, while ileal Jmax was normalized 12 h following a single insulin injection. The normalization of Na-K ATPase activity lagged behind Na-dependent glucose transport regulation by 24 h in both jejunum and ileum. Brush border surface area was increased in the ileum of diabetic rats as a result of an increase in microvillus height. Insulin treatment resulted in a decrease in ileal microvillus height to control values by 12 h, which correlated directly with the decrease in Na-dependent glucose transport. Insulin had no effect on jejunal brush border surface area. In conclusion, these findings indicate that the jejunum and ileum respond differentially to experimentally induced diabetes, and these regions also utilize different adaptive mechanisms to regulate Na-dependent glucose transport.

The effect of insulin on intestinal sodium-dependent glucose transport and brush border membrane surface area was examined in male Sprague-Dawley rats following a 30-day period of nontreated streptozocin-induced diabetes. Nontreated diabetic rats were hyperglycemic and demonstrated increased jejunal and ileal Na-dependent glucose transport Jmax (maximal transport capacity) and Na-K ATPase activity compared with controls. Daily administration of insulin resulted in a steady decline in blood glucose levels over a period of 6 days. Jejunal Jmax was normalized after 2 days of insulin therapy, while ileal Jmax was normalized 12 h following a single insulin injection. The normalization of Na-K ATPase activity lagged behind Na-dependent glucose transport regulation by 24 h in both jejunum and ileum. Brush border surface area was increased in the ileum of diabetic rats as a result of an increase in microvillus height. Insulin treatment resulted in a decrease in ileal microvillus height to control values by 12 h, which correlated directly with the decrease in Na-dependent glucose transport. Insulin had no effect on jejunal brush border surface area. In conclusion, these findings indicate that the jejunum and ileum respond differentially to experimentally induced diabetes, and these regions also utilize different adaptive mechanisms to regulate Na-dependent glucose transport.

SummaryThe effect of oral vanadate on intestinal sodium-dependent glucose transport and 6-phosphofructo-l-kinase (EC 2.7.1.11) activity was examined in male Sprague-Dawley rats following a 30-day period of non-treated streptozotocin-induced diabetes. Non-treated diabetic rats were hyperglycaemic and demonstrated increased intestinal sodium-dependent glucose transport and Na,K-ATPase activity compared with controls. These increases were associated with a significant decrease in the total activity and activity ratios (activity at 0.5 mmol/1 fructose 6-phosphate at pH 7.0/activity at pH 8.0) of intestinal 6-phosphofructo-l-kinase and decreased levels of fructose 2,6-bisphosphate. Supplementation of drinking water with vanadate (0.5 mg/ml) resulted in a rapid decline in blood glucose levels to a slightly hyperglycaemic level. Jejunal glucose transport and Na,KATPase activity were normalized after 48 h of vanadate treatment. In contrast, ileal glucose transport was significantly reduced 12 h following beginning vanadate treatment even though Na,K-ATPase activity did not normalize until 36 h later. K m was significantly decreased in both jejunum and ileum by vanadate treatment indicating an increased affinity of the sodium-dependent intestinal glucose transporter for glucose. 6-phosphofructo-l-kinase total activity and susceptibility to ATP inhibition was completely restored after 12 h of vanadate treatment. This increase was associated with a rise in fructose 2,6-bisphosphate levels. Fasting rats for 12 h had no effect on glucose transport or 6-phosphofructo-l-kinase activity, indicating the anorectic effect of vanadate was not responsible for changes in either parameter. In contrast, cycloheximide prevented both the rise in 6-phosphofructo-l-kinase activity and the rise in fructose 2,6-bisphosphate levels, and the subsequent reduction in glucose transport, indicating a requirement for protein synthesis. The removal of vanadate resulted in an immediate return to pre-treatment blood glucose levels. In contrast, intestinal glucose transport and 6-phosphofructo-l-kinase activity remained at treatment levels up until 72 h, indicating that oral vanadate treatment can have prolonged beneficial effects on intestinal function. In conclusion, the treatment of streptozotocin-induced diabetic rats with oral vanadate results in an activation of 6-phosphofructo-l-kinase coupled with a normalization of intestinal sodium-dependent glucose transport. Vanadate may thus have a beneficial effect on intestinal function and may prove useful as oral adjunctive diabetic therapy. [Diabetologia (1995) 38: 403-412]