This study was initiated to see if the insulin resistance, hyperinsulinemia, and hypertension that follow feeding normotensive Sprague-Dawley rats a fructose-rich diet could be prevented by letting rats run spontaneously in exercise wheel cages. Blood pressure in sedentary rats increased from (mean +/- SEM) 125 +/- 2 to 148 +/- 3 mm Hg in response to 2 weeks of a high fructose diet, and this increment was significantly (p less than 0.001) attenuated in exercising rats (from 121 +/- 1 to 131 +/- 2 mm Hg). In addition, mean (+/- SEM) plasma insulin concentration was lower in fructose-fed rats allowed to run spontaneously (44 +/- 2 vs 62 +/- 5 microU/ml; p less than 0.01). Finally, resistance to insulin-stimulated glucose uptake was assessed by determining the steady state plasma glucose response to a continuous glucose and exogenous insulin infusion during a period in which endogenous insulin secretion was suppressed. The results of these studies indicated that the mean (+/- SEM) steady state plasma glucose concentration was significantly lower in the exercise-trained rats (127 +/- 5 vs 168 +/- 6 mg/dl; p less than 0.001), despite the fact that the steady state plasma insulin levels were also lower in rats allowed to run spontaneously (75 +/- 4 vs 90 +/- 5 microU/ml; p less than 0.05). Thus, the ability of exercise-trained rats to stimulate glucose disposal was enhanced as compared with that of sedentary rats fed the same fructose-rich diet. These data demonstrate that the insulin resistance, hyperinsulinemia, and hypertension produced in normotensive rats by feeding them a high fructose diet can be attenuated if rats are allowed to run spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)

Fructose metabolism is generally held to occur essentially in cells of the small bowel, the liver, and the kidneys expressing fructolytic enzymes (fructokinase, aldolase B and a triokinase). In these cells, fructose uptake and fructolysis are unregulated processes, resulting in the generation of intracellular triose phosphates proportionate to fructose intake. Triose phosphates are then processed into lactate, glucose and fatty acids to serve as metabolic substrates in other cells of the body. With small oral loads, fructose is mainly metabolized in the small bowel, while with larger loads fructose reaches the portal circulation and is largely extracted by the liver. A small portion, however, escapes liver extraction and is metabolized either in the kidneys or in other tissues through yet unspecified pathways. In sedentary subjects, consumption of a fructose-rich diet for several days stimulates hepatic de novo lipogenesis, increases intrahepatic fat and blood triglyceride concentrations, and impairs insulin effects on hepatic glucose production. All these effects can be prevented when high fructose intake is associated with increased levels of physical activity. There is also evidence that, during exercise, fructose carbons are efficiently transferred to skeletal muscle as glucose and lactate to be used for energy production. Glucose and lactate formed from fructose can also contribute to the re-synthesis of muscle glycogen after exercise. We therefore propose that the deleterious health effects of fructose are tightly related to an imbalance between fructose energy intake on one hand, and whole-body energy output related to a low physical activity on the other hand.

The study was aimed to examine if oral administration of the aqueous extract of the whole plant OCIMUM SANCTUM (OS) protects against the development of insulin resistance in fructose fed rats. Male Wister rats were randomly divided into four groups of eight animals each: group-S (starch diet), group-F (fructose diet), group-F+OS (fructose diet along with OCIMUM SANCTUM extract at a dose of 200 mg/kg), group-S+OS (starch diet along with OCIMUM SANCTUM). During the experimental period of 60 days body weight, plasma glucose, insulin, and triglycerides were measured at an interval of 15 days. Insulin sensitivity was assessed at the end of experimental period by measuring glucose-insulin index, which is the product of the areas under the curve of glucose and insulin during oral glucose tolerance test. The nontoxic nature of OS was revealed by unaltered body weight, plasma glucose, insulin, and triglyceride levels in group-S+OS when compared with group-S. A significant gain in body weight, hyperglycemia, hyperinsulinemia, hypertriglyceridemia, and insulin resistance were observed in group-F when compared with group-S. OS treatment prevented the observed fructose induced alterations in group-F+OS. In conclusion, our results suggests that oral administration of OS aqueous extract could delay the development of insulin resistance in rats and may be used as an adjuvant therapy for treating diabetic patients with insulin resistance.

The aim of this study was to identify the role of thioredoxin-interacting protein (TXNIP) and its interaction with antioxidants in the activation of the fructose-induced NOD-like receptor protein 3 (NLRP3) inflammasome in human macrophages. The study was performed with U937 and THP-1 macrophage cell lines. Total reactive oxygen species (ROS) were measured by flow cytometry. Interleukin-1β (IL-1β), IL-18, NLRP3, TXNIP, and caspase-1 protein expression was detected using western blotting. Quantitative real-time polymerase chain reaction was used to detect IL-1β, IL-18, and caspase-1 gene expression. Intracellular shuttling of TXNIP was assessed by immunofluorescent staining with MitoTracker Red. Increased production of ROS and expression of IL-1β, IL-18, and caspase-1 genes and proteins were observed in U937 and THP-1 cells incubated with fructose and were effectively inhibited by quercetin and ascorbic acid. Intracellular shuttling of TXNIP from the nucleus into the mitochondria was detected under stimulation with fructose, which was also attenuated by antioxidants quercetin and ascorbic acid but not butylated hydroxyanisole. Treatment of macrophages with fructose promoted the association between TXNIP and NLRP3 in the cytosol, sequentially resulting in the activation of the NLRP3 inflammasome. This study revealed that intracellular TXNIP protein is a critical regulator of activation of the fructose-induced NLRP3 inflammasome, which can be effectively blocked by the antioxidants quercetin and ascorbic acid.