Vmax For Glucose Transport Research Articles

Effects of high-fat diet on glucose metabolism in isolated pancreatic acini of rats.

The purpose of the present study was to document the metabolism of glucose and its responsiveness to insulin in isolated pancreatic acini from rats fed either a low- or high-fat diet. The different steps investigated were labeled glucose oxidation, lactate production, hexokinase activity, and glucose transport, which was assessed by using both 3-O-methylglucose and 2-deoxyglucose. The acinar capacity to metabolize glucose (sum of CO2 plus lactate) was decreased by 50% by feeding the rats a high-fat diet. The impairment of glucose metabolism could not be explained by a defect in the glucose phosphorylation step because hexokinase activity was not changed in isolated acini from rats fed a high-fat diet. The effect of a high-fat diet was entirely accounted for by a reduction in the glucose transport rate that was achieved through a decrease in glucose transport Vmax with no change in Km. We could not detect any effect of insulin on glucose metabolism or 2-deoxyglucose uptake, whatever the diet composition. This work establishes that a high-fat diet, known to markedly alter pancreatic exocrine enzymes, also induces a large decrease in acinar glycolytic flux, raising the question of the relation between these two sets of adaptive changes.

Effect of intravenous somatostatin on jejunal absorption of glucose, amino acids, water, and electrolytes

Somatostatin has previously been reported to reduce plasma levels of sugars and triglycerides following oral test meals. This study was designed to answer the question as to whether or not somatostatin affects transport directly by inhibiting absorption across the mucosa of the small bowel. Steady-state perfusion experiments with either glucose- and amino acid-containing test solutions or a plasmalike electrolyte solution were carried out in the jejunum of healthy subjects. During the intestinal perfusion either saline (control) or somatostatin (8 μg/ kg/h) was infused for 90 min through a peripheral vein. Somatostatin infusion significantly reduced glucose absorption, and kinetic analysis revealed that this effect was mainly due to a reduction of Vmax of glucose transport. Amino acid absorption (l-glycine and l-lysine) was also reduced by somatostatin infusion. Despite a significant decrease in undirectional water fluxes and calculated rate of water and urea diffusion, somatostatin did not affect net water or electrolyte absorption when the plasma-like electrolyte solution was perfused. These studies suggest that somatostatin inhibits glucose and amino acid absorption by a direct effect on the intestinal mucosa. Although the mechanism is unknown, we think that somatostatin most likely causes its effect by a selective reduction of functional mucosal surface area of the intestine.

Ability of circulating insulin to chronically regulate the cellular glucose transport system

We have tested the idea that the circulating plasma insulin level plays an important role in the long-term regulation, or maintenance, of the cellular glucose transport system, distinct from insulin's ability to acutely accelerate glucose transport. To study this hypothesis, groups of rats were made either hyperinsulinemic or hypoinsulinemic by daily insulin injections or Streptozotocin treatment, respectively. Different levels of hypoinsulinemia were produced by using different doses of Streptozotocin (40 and 55 mg/kg). Isolated adipocytes were prepared from each animal and glucose transport was assessed by measuring the initial rates of uptake of the nonmetabolyzable hexose 2-deoxy glucose. In cells from control animals, the Vmax of in vitro adipocyte glucose transport was 7.1 +/- 0.7 nmole/min/10(6) cells in the basal state and 22.9 +/- 0.9 nmole/min/10(6) cells in the presence of a maximally effective insulin concentration (25 ng/ml) in the buffer. In cells from the experimentally hyperinsulinemic animals, these Vmax values were increased to 11.7 +/- 0.8 and 44.2 +/- 1.1 nmole/min/10(6) cells. Using adipocytes from both groups of Streptozotocin treated (high dose, 55 mg/kg, low dose, 40 mg/kg) insulin deficient diabetic animals, Vmax values were found to be progressively decreased. Thus, in the low dose group, basal and insulin stimulated Vmax values were 1.6 +/- 0.5 and 5.7 +/- 0.7 nmole/min/10(6) cells, as compared to values of 0.9 +/- 0.2 and 1.7 +/- 0.6 in the high dose group. Furthermore, when hyperinsulinemia was induced by feeding rats high carbohydrate diets for 10 days, adipocyte glucose transport Vmax increased 50%. In contrast, when hypoinsulinemia was achieved by fasting rats for 72 hr, transport Vmax decreased by 50%. The apparent Km for 2-deoxy glucose uptake was the same under all conditions. In conclusion, assuming that the Vmax of transport is some function of the number of glucose transport carriers per cell, then these results support the hypothesis that in addition to acute acceleration of glucose transport, insulin is also an important long-term regulator of the number of available adipocyte glucose transport carriers.