Oral vanadate reduces Na(+)-dependent glucose transport in rat small intestine.

The effects of oral vanadate supplementation on intestinal morphometry and glucose transport were examined in STZ-induced diabetic and age-matched control male Sprague-Dawley rats. Animals received 0.1 mg/ml vanadium pentoxide in their drinking water over 14 days. Vanadate reduced intestinal glucose maximal transport capacity in both diabetic and control animals. In jejunum tissue, this decrease in glucose absorption was a direct consequence of downregulation of the glucose carrier and was not related to changes in mucosal morphometry. In the ileum tissue of control animals, the vanadate-induced decrease in glucose maximal transport capacity occurred in conjunction with an increase in carrier affinity and mucosal morphometric measurements. In the ileum tissue of diabetic animals, the vanadate-induced decrease in glucose maximal transport capacity occurred with a decrease in mucosal morphometric measurements. Na(+)-K(+)-adenosine triphosphatase activity was affected by vanadate only in diabetic animals. These results demonstrate that oral vanadate supplementation results in downregulation of the small intestinal sodium-dependent glucose carrier in both diabetic and nondiabetic rats. Furthermore, the vanadate effect may be occurring at the cellular level.

Adaptation of intestinal glucose transport in rats with diabetes mellitus occurs independent of hyperphagia.

Chronic diabetes enhances intestinal absorption of glucose and induces hyperphagia. We examined the enhanced intestinal absorption of glucose in ad libitum-fed rats with streptozocin-induced diabetes mellitus and compared these results with those obtained from pair-fed diabetic animals. Maximal transport capacity (Vmax) and carrier affinity (K0.5) were determined by measuring jejunal and ileal short circuit current (Isc) responses to varying concentrations of 3-O-methyl-D-glucopyranose and D-glucose. Pair-fed diabetic animals maintained the same body weight as animals fed ad libitum, although ad libitum-fed diabetic rats had an increased oral chow intake. Age-matched control rats maintained a constant jejunal and ileal Vmax and K0.5 throughout the study. Diabetic rats fed ad libitum demonstrated an enhanced Vmax and K0.5 in both jejunum and ileum. Pair feeding diabetic animals further enhanced jejunal Vmax while lowering jejunal K0.5 levels. In contrast, pair feeding diabetic animals delayed and blunted changes in ileal Vmax and prevented changes in ileal K0.5. In conclusion, signals other than those of hyperphagia regulate kinetic changes in glucose absorption during diabetes mellitus. Furthermore, these changes have differing effects on jejunum and ileum.

Vanadate reduces sodium-dependent glucose transport and increases glycolytic activity in LLC-PK1 epithelia.

The effect of vanadate pentoxide on apical sodium-dependent glucose transport in LLC-PK1 epithelia was examined. Epithelia grown in the presence or absence of 1 microM vanadate formed confluent monolayers and exhibited no differences in DNA, protein, or ultrastructure. Vanadate-supplemented epithelia demonstrated a lower steady-state alpha-methyl-D-glucopyranoside (AMG) concentrating capacity and a twofold reduction in apical AMG uptake Jmax. This decreased AMG transport occurred as a consequence of a reduction in the number of transport carriers and was not associated with a change in the sodium electrochemical gradient. The vanadate-induced reduction in apical glucose carrier functional activity and expression was accompanied by a stimulation of intracellular glycolytic flux activity, as evidenced by increased glucose consumption, lactate production, PFK-1 activity, and intracellular ATP. There was no difference in intracellular cAMP levels between vanadate-supplemented and non-supplemented epithelia. These results demonstrate an association between stimulation of glycolytic pathway activity and an adaptive response in the form of a reduction in the function and expression of the sodium-dependent apical glucose transporter in LLC-PK1 epithelia.

Altered glucose carrier expression: mechanism of intestinal adaptation during streptozocin-induced diabetes in rats.

Intestinal adaptation of glucose transport during streptozocin-induced diabetes in rats was examined using microdensitometric analysis of [3H]phlorizin binding. Results of specific phlorizin binding were correlated with measurements of maximal transport capacity, carrier affinity, villus height, and enterocyte birth rate determined by the metaphase arrest technique. Animals diabetic for 14 days (acute) and 60 days (chronic) were compared with age-matched controls. In the jejunum, adaptation occurred only in chronically diabetic rats and consisted of a 10-fold increase in the density of phlorizin binding sites in the upper villus region (i.e., that portion normally transporting glucose), while in the ileum, adaptation occurred both in acute and chronically diabetic rats and consisted of 1) a 3-fold increase in density of phlorizin binding sites in the upper villus region of acutely diabetic rats and 2) an increased density in the upper villus region as well as the recruitment of phlorizin binding sites in the mid to lower villus region (i.e., that portion not normally transporting glucose) of chronically diabetic rats. Enhancement of glucose Vmax and villus length accompanied changes in binding, whereas enterocyte birth rates were similar in each group.