Dietary leucine--an environmental modifier of insulin resistance acting on multiple levels of metabolism

Environmental factors, such as the macronutrient composition of the diet, can have a profound impact on risk of diabetes and metabolic syndrome. In the present study we demonstrate how a single, simple dietary factor--leucine--can modify insulin resistance by acting on multiple tissues and at multiple levels of metabolism. Mice were placed on a normal or high fat diet (HFD). Dietary leucine was doubled by addition to the drinking water. mRNA, protein and complete metabolomic profiles were assessed in the major insulin sensitive tissues and serum, and correlated with changes in glucose homeostasis and insulin signaling. After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation, as well as alterations in metabolomic profile of amino acid metabolites, TCA cycle intermediates, glucose and cholesterol metabolites, and fatty acids in liver, muscle, fat and serum. Doubling dietary leucine reversed many of the metabolite abnormalities and caused a marked improvement in glucose tolerance and insulin signaling without altering food intake or weight gain. Increased dietary leucine was also associated with a decrease in hepatic steatosis and a decrease in inflammation in adipose tissue. These changes occurred despite an increase in insulin-stimulated phosphorylation of p70S6 kinase indicating enhanced activation of mTOR, a phenomenon normally associated with insulin resistance. These data indicate that modest changes in a single environmental/nutrient factor can modify multiple metabolic and signaling pathways and modify HFD induced metabolic syndrome by acting at a systemic level on multiple tissues. These data also suggest that increasing dietary leucine may provide an adjunct in the management of obesity-related insulin resistance.     

Comparative effectiveness of carvedilol and propranolol on glycemic control and insulin resistance associated with L-thyroxin-induced hyperthyroidism--an experimental study

The present study was undertaken to investigate the effectiveness of adrenergic antagonists carvedilol and propranolol on L-thyroxin-induced cardiovascular and metabolic disturbances in rats. Treatment with L-thyroxin sodium (75 mg/kg body mass, s.c., every alternate day for 3 weeks), produced a significant increase in food and water intake, body temperature, heart rate, systolic blood pressure, along with an increase in serum T3, T4, and triglyceride levels. Besides a significant reduction in body mass, serum levels of TSH and cholesterol were also reduced following L-thyroxin treatment. Carvedilol (10 mg/kg body mass, orally) and propranolol (10 mg/kg body mass, i.p.) administered daily in the third week to 2 separate groups of L-thyroxin-treated animals reversed thyroxin-induced loss in body mass and rise in body temperature, blood pressure, and heart rate. Propranolol treatment increased TSH levels and decreased T3 and T4 levels in hyperthyroid animals, whereas carvedilol did not produce any effect on thyroid hormones. Carvedilol treatment reversed thyroxin induced hypertriglyceridemia, whereas propranolol treatment had no effect. Both carvedilol and propranolol prevented decrease in cholesterol levels induced by thyroxine. Compared with normal animals, L-thyroxin-treated animals showed a state of hyperglycemia, hyperinsulinaemia, impaired glucose tolerance, and insulin resistance, as inferred from elevated fasting serum glucose and insulin levels, higher area under the curve over 120 min for glucose, and decreased insulin sensitivity index (KITT). Propranolol and carvedilol treatment significantly decreased fasting serum glucose levels. Treatment with propranolol did not alter serum insulin levels, area-under-the-curve glucose, or KITT values. However, treatment with carvedilol significantly reduced area-under-the-curve glucose, decreased fasting serum insulin levels and significantly increased KITT values. In conclusion, carvedilol appears to produce favorable effects on insulin sensitivity and glycemic control and can therefore be considered as more efficacious adjunctive treatment than propranolol in hyperthyroidism.     

Testosterone deficiency impairs glucose oxidation through defective insulin and its receptor gene expression in target tissues of adult male rats

Testosterone and insulin interact in their actions on target tissues. Most of the studies that address this issue have focused on the physiological concentration of testosterone, which maintains normal insulin sensitivity but has deleterious effects on the same when the concentration of testosterone is out of this range. However, molecular basis of the action of testosterone in the early step of insulin action is not known. The present study has been designed to assess the impact of testosterone on insulin receptor gene expression and glucose oxidation in target tissues of adult male rat. Adult male albino rats were orchidectomized and supplemented with testosterone (100 microg/100 g b. wt., twice daily) for 15 days from the 11th day of post orchidectomy. On the day after the last treatment, animals were euthanized and blood was collected for the assay of plasma glucose, serum testosterone and insulin. Skeletal muscles, such as gracilis and quadriceps, liver and adipose tissue were dissected out and used for the assay of various parameters such as insulin receptor concentration, insulin receptor mRNA level and glucose oxidation. Testosterone deprivation due to orchidectomy decreased serum insulin concentration. In addition to this, insulin receptor number and its mRNA level and glucose oxidation in target tissues were significantly decreased (p<0.05) when compared to control. However, testosterone replacement in orchidectomized rats restored all these parameters to control level. It is concluded from this study that testosterone deficiency-induced defective glucose oxidation in skeletal muscles, liver and adipose tissue is mediated through impaired expression of insulin and its receptor gene.     

Metabolic interactions of dichloroacetate and insulin in experimental diabetic ketoacidosis.

1. The infusion of sodium dichloroacetate into rats with severe diabetic ketoacidosis over 4h caused a 2mM decrease in blood glucose, and small falls in blood lactate and pyruvate concentrations. Similar findings had been reported in normal rats (Blackshear et al., 1974). In contrast there was a marked decrease in blood ketone-body concentration in the diabetic ketoacidotic rats after dichloroacetate treatment. 2. The infusion of insulin alone rapidly decreased blood glucose and ketone bodies, but caused an increase in blood lactate and pyruvate. 3. Dichloroacetate did not affect the response to insulin of blood glucose and ketone bodies, but abolished the increase of lactate and pyruvate seen after insulin infusion. 4. Neither insulin nor dichloroacetate stimulated glucose disappearance after functional hepatectomy, but both agents decreased the accumulation in blood of lactate, pyruvate and alanine. 5. Dichloroacetate inhibited 3-hydroxybutyrate uptake by the extra-splachnic tissues; insulin reversed this effect. Ketone-body production must have decreased, as hepatic ketone-body content was unchanged by dicholoracetate yet blood concentrations decreased. 6. It was concluded that: (a) dichloroacetate had qualitatively similar effects on glucose metabolism in severely ketotic rats to those observed in non-diabetic starved animals; (b) insulin and dichloroacetate both separately and together, decreased the net release of lactate, pyruvate and alanine from the extra-splachnic tissues, possibly through a similar mechanism; (c) insulin reversed the inhibition of 3-hydroxybutyrate uptake caused by dichloroacetate; (d) dichloroacetate inhibited ketone-body production in severe ketoacidosis.     

Effects of resveratrol on the amelioration of insulin resistance in KKAy mice

Resveratrol (Res) has attracted great interest regarding its effects related to metabolic syndrome, especially for lipid metabolic disorder or insulin resistance; however, the underlying mechanisms remain elusive. To explore the effects of Res on insulin sensitivity and the underlying mechanism, insulin-resistant KKA(y) mice were treated with 2?and 4?g/kg diets of Res for 12?weeks. After the treatment, blood glucose, serum insulin, glucose tolerance, and insulin tolerance, as well as other indices such as adiponectin mRNA in epididymal adipose tissues, silent information regulator 1 (Sirt1), AMP-activated protein kinase (AMPK), insulin receptor substrate 1 (IRS1), and phosphorylated protein kinase B (PKB/AKT) proteins in liver and soleus muscles, were investigated. The results indicate that Res intervention reduces blood glucose and serum insulin levels, improves insulin and glucose tolerance, increases serum adiponectin and adiponectin mRNA levels in epididymal adipose tissues, and more importantly, elevates Sirt1, p-AMPK, p-IRS1, and p-AKT levels in liver and soleus muscles. In conclusion, Res could improve insulin sensitivity and ameliorate insulin resistance in KKA(y) mice, which may be associated with the upregulation of Sirt1 protein in liver and soleus muscles and consequent AMPK activation, as well as insulin-signaling related proteins.     

Hypoglycémie spontanée et insuffisance rénale chronique.

Although glucose intolerance occurs as a consequence of chronic renal failure, improvement of a diabetic state by deterioration of renal function is a well known phenomenon. Recently occasional cases of spontaneous hypoglycemia in patients with chronic renal failure have been reported; two such cases and the results of metabolic studies are described in this paper. Pituitary, thyroid and adrenal function appeared to be normal. The results of an oral glucose tolerance test were normal; an appropriate insulin response was demonstrated in one patient, and a slightly elevated basal insulin value with a delayed insulin response to oral administration of glucose was demonstrated in the other. An insulin tolerance test did not support the hypothesis of increased insulin sensitivity as a factor, and the growth hormone response to hypoglycemia was normal. An intravenous glucagon test caused a subnormal increase in plasma glucose concentration, and the intravenous administration of tolbutamide produced hypoglycemia without an increase insulin sensitivity as a factor, and the growth hormone response to hypoglycemia was normal. An intravenous glucagon test caused a subnormal increase in plasma glucose concnetration, and the intravenous administration of tolbutamide produced hypoglycemia without an increase in insulin values. The plasma alanine concentration was low and the proinsulin/insulin ratio was increased. The origin of this hypoglycemia is not clear but is probably multifactorial. However, low hepatic glycogen stores and inadequate gluconeogenesis due to substrate deficiency seem to be involved.     

Betaine Down Regulates Apelin Gene Expression in Cardiac and Adipose Tissues of Insulin Resistant Diabetic Rats Fed by High-Calorie Diet

Apelin is a newly discovered peptide that its serum level increases in diabetic patients with cardiovascular dysfunction. Recent studies indicate the beneficial actions of betaine in reducing the cardiovascular and metabolic complications, however data related to its effect on adipocytokine expression is limited. The aim of this study was to evaluate the effect of betaine supplementation on Apelin gene expression in cardiac muscle and adipose tissue of insulin resistance, diabetic rats fed by a high calorie diet. To induce insulin resistance rats were fed with high fat/high carbohydrate diet for five weeks and then 30 mg/kg STZ was injected intraperitoneally. After confirming of diabetes incidence (serum glucose above 7.5 mmol/l) the animals were treated with 1 % betaine in drinking water for 28 days. At days 14 and 28 after treatment, animals were euthanized and Apelin gene expression was evaluated by real time PCR and western blot in heart and adipose tissues. Serum levels of insulin, Apelin and glucose and HOMA–IR were also measured. Our results showed that feeding of rats by a high calorie diets caused insulin resistance, which was manifested by elevated plasma insulin, glucose and Apelin levels and also HOMA–IR. Apelin gene expression in heart and adipose tissues were significantly increased simultaneously with the progression of diabetes. Betaine supplementation decreased serum Apelin and down regulated Apelin expression in adipose tissue and cardiac muscle, particularly at day 28 of treatment. We concluded that betaine might improve metabolic and cardiovascular complications in diabetic patients by regulation of Apelin expression and secretion.     

Significant Improvement of Insulin Resistance of GK Rats by Treatment with Sodium Selenate

We studied the effect of sodium selenate on insulin resistance of Goto-Kakizaki (GK) rats. Rats were kept on standard laboratory chow with and without i.p. injections of sodium selenate (0.173 mg/kg body weight) for 14 days, and then subjected to the glucose clamp. The glucose clamp studies confirmed an improvement in insulin-stimulated glucose disposal in GK rats treated with sodium selenate, with respect to both insulin sensitivity and responsiveness. This amelioration of insulin resistance may be partly due to a direct effect of the sodium selenate on peripheral tissues. 2-Deoxyglucose uptake in sodium selenate-treated adipocytes was increased and the insulin findings suggest that sodium selenate increases not only insulin sensitivity but also insulin responsiveness. Sodium selenate also accelerated glucose incorporation into adipocytes of rats, suggesting that the action of sodium selenate is peripheral. Interestingly, sodium selenate at a high concentration (about 1 mmol/L) was more effective than insulin in enhancing glucose uptake. The present study suggested that sodium selenate treatment led to substantial improvement in peripheral insulin resistance.     

Effect of parathyroid hormone on the increase in serum glucose and insulin levels after a glucose load to thyroparathyroidectomized rats.

Thyroparathyroidectomy (TPTX) caused a significant increase in serum glucose and a corresponding fall in serum calcium in both fed and fasted rats. The increase in serum glucose, induced by TPTX, was markedly potentiated by a single intraperitoneal administration of calcium (2 mg/100 g BW) which caused a significant elevation of serum calcium in thyroparathyroidectomized rats. Parathyroid hormone (PTH; 20 U/100 g BW) administered subcutaneously to thyroparathyroidectomized rats, caused a significant decrease in serum glucose (0.1 g/100 g BW) to sham-operated rats significantly increased both serum glucose and insulin. The rise of serum glucose produced by a glucose load was markedly potentiated by TPTX, but the increase in serum insulin was not promoted significantly. The administration of PTH decreased both serum glucose and insulin levels increased by a glucose load to thyroparathyroidectomized rats, in a dose-dependent manner. The administration of calcitonin (80 MRC mU/100 g BW) significantly prevented the effect of PTH to decrease serum glucose after a glucose load to thyroparathyroidectomized rats, and calcitonin increased serum insulin. These results suggest that the effect of PTH on serum glucose does not involve insulin secretion.     

Enhanced potential for oxidative stress in hyperinsulinemic rats: imbalance between hepatic peroxisomal hydrogen peroxide production and decomposition due to hyperinsulinemia.

Oxidative stress is involved in aging and age-related diseases. Several metabolic alterations similar to those encountered with aging and age-related diseases have been observed in response to hyperinsulinemia. Surprisingly, this metabolic derangement diminished hepatic peroxisomal beta-oxidation which is a major source of H2O2 production in the liver, suggesting a protective effect against oxidative stress. However, the impact of hyperinsulinemia on the balance between H2O2 production and elimination in the liver is not known. Consequently, this study was undertaken to evaluate the effect of sustained high serum insulin levels on the activity of hepatic catalase, a peroxisomal antioxidant enzyme involved in the decomposition of H2O2. Male Sprague-Dawley rats received intravenous infusion of either 30% glucose, 30% galactose or normal saline for seven days. Activity of hepatic peroxisomal beta-oxidation and catalase decreased 58% and 74%, respectively, in glucose-infused rats compared with galactose- or saline-infused animals. When infused simultaneously with glucose, diazoxide blocked glucose-enhanced insulin secretion and prevented the decrease in peroxisomal enzyme activities, without altering blood glucose concentration. Neither diazoxide alone nor galactose, which did not alter serum insulin levels, had any effect on enzyme activities. These results suggest that hyperinsulinemia is responsible for the decreased enzyme activities observed in glucose-infused rats. Indeed, a strong negative correlation between serum insulin levels and hepatic peroxisomal enzyme activities was found. To investigate the mechanism by which insulin modulates catalase activity, we studied rates of synthesis and degradation of catalase in saline- and glucose-infused rats. Data show that insulin diminishes rates of catalase synthesis, while exhibiting no effect on its degradation. Upsetting the balance between the cellular capacity to produce and eliminate H2O2 may be a contributing factor to the known deleterious effects of hyperinsulinemia.     

Insulin and Non-esterified Fatty Acid Metabolism in Asymptomatic Diabetics and Atherosclerotic Subjects

Glucose, insulin and non-esterified fatty acid (NEFA) metabolism was studied in 18 patients (mean age 49) with ischemic heart disease (IHD) who did not have any concurrent disorder known to affect glucose tolerance.Significant hyperglycemia and hyperinsulinemia were observed in the IHD patients after oral glucose. The serum NEFA declined to a lower level in IHD patients than in normal subjects who received glucose.In response to hypoglycemia following the oral administration of sodium tolbutamide the serum NEFA in IHD patients rose to a higher level in the rebound phase than in normal subjects. This rise was preceded by a sharp decline in the concentration of circulating insulin.In 72% of the patients (IHD sub-group) the blood glucose values after oral glucose satisfied the criteria for the diagnosis of diabetes mellitus. The metabolic changes following oral glucose in the IHD sub-group and in asymptomatic diabetics (AD), free of clinical atherosclerosis and with similar impairment in glucose tolerance, were compared. Despite insignificantly lower insulin concentrations, the AD showed a significantly lesser fall in circulating NEFA than did the patients in the IHD sub-group. After oral sodium tolbutamide the IHD sub-group patients showed a greater insulin response and a greater rebound increase in circulating NEFA than did the AD.These differences in response to oral glucose and to sodium tolbutamide suggest that the pathogenesis of the impaired glucose tolerance in IHD may be different from that responsible for abnormal carbohydrate tolerance in asymptomatic diabetics without evident atherosclerosis. The abnormalities demonstrated in glucose, insulin and NEFA metabolism may play a role in the genesis of the hyperlipoproteinemia and atherosclerosis of IHD. One possible mechanism leading to hyperlipoproteinemia in ischemic heart disease compatible with the data is discussed.     

Reduction of low molecular weight protein-tyrosine phosphatase expression improves hyperglycemia and insulin sensitivity in obese mice

To investigate the role of low molecular weight protein-tyrosine phosphatase (LMW-PTP) in glucose metabolism and insulin action, a specific antisense oligonucleotide (ASO) was used to reduce its expression both in vitro and in vivo. Reduction of LMW-PTP expression with the ASO in cultured mouse hepatocytes and in liver and fat tissues of diet-induced obese (DIO) mice and ob/ob mice led to increased phosphorylation and activity of key insulin signaling intermediates, including insulin receptor-beta subunit, phosphatidylinositol 3-kinase, and Akt in response to insulin stimulation. The ASO-treated DIO and ob/ob animals showed improved insulin sensitivity, which was reflected by a lowering of both plasma insulin and glucose levels and improved glucose and insulin tolerance in DIO mice. The treatment did not decrease body weight or increase metabolic rate. These data demonstrate that LMW-PTP is a key negative regulator of insulin action and a potential novel target for the treatment of insulin resistance and type 2 diabetes.     

Changes in Serum Adiponectin in Mice Chronically Exposed to Inorganic Arsenic in Drinking Water

Cardiovascular disease and diabetes mellitus are prominent features of glucose and lipid metabolism disorders. Adiponectin is a key adipokine that is largely involved in glucose and lipid metabolism processes. A growing body of evidence suggests that chronic exposure to inorganic arsenic is associated with cardiovascular disease and diabetes mellitus. We hypothesized that arsenic exposure may increase the risk of cardiovascular disease and diabetes mellitus by affecting the level of adiponectin. In this study, we examined serum adiponectin levels, as well as serum levels of metabolic measures (including fasting blood glucose, insulin, total cholesterol, triglyceride, and high-density lipoprotein (HDL)-cholesterol) in C57BL/6 mice exposed to inorganic arsenic in drinking water (5 and 50 ppm NaAsO₂) for 18 weeks. Body mass and adiposity were monitored throughout the study. We found no significant changes in serum insulin and glucose levels in mice treated with arsenic for 18 weeks. However, arsenic exposure decreased serum levels of adiponectin, triglyceride, and HDL-cholesterol. Further, an inverse relationship was observed between urinary concentrations of total arsenic and serum levels of adiponectin. This study suggests that arsenic exposure could disturb the metabolism of lipids and increase the risk of cardiovascular disease by reducing the level of adiponectin.     

Exercise-induced increase in muscle insulin sensitivity.

Exercise/muscle contraction activates glucose transport. The increase in muscle glucose transport induced by exercise is independent of insulin. As the acute effect of exercise on glucose transport wears off, it is replaced by an increase in insulin sensitivity. An increase in insulin sensitivity results in a shift in the insulin dose-response curve to the left, with a decrease in the concentration of insulin needed to induce 50% of the maximal response. This phenomenon, which plays a major role in rapid muscle glycogen accumulation after exercise, is not mediated by amplification of the insulin signal. Development of the increase in insulin sensitivity after contractions does not require protein synthesis or activation of p38 MAPK. It does require the presence of a serum protein during the period of contractile activity. The effect of exercise on muscle insulin sensitivity is mimicked by hypoxia and by treatment of muscles with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside to activate AMP-activated protein kinase. The postexercise increase in sensitivity of muscle glucose transport to activation is not specific for insulin but also involves an increased susceptibility to activation by a submaximal contraction/hypoxia stimulus. The increase in insulin sensitivity is mediated by translocation of more GLUT4 glucose transporters to the cell surface in response to a submaximal insulin stimulus. Although the postexercise increase in muscle insulin sensitivity has been characterized in considerable detail, the basic mechanisms underlying this phenomenon remain a mystery.     

Characteristics of the inhibitory effect of alkalosis on insulin secretion

Glucose-induced insulin secretion by the perfused sodium pentobarbital-anesthetized-rat pancreases was studied under different extracellular pH ranging from 7.4 to 7.8. Under our experimental conditions the amount of insulin released was inversely correlated to the pH increase. Besides, metabolic (CO2H- excess) or gaseous (low pCO2) type of alkalosis, were equally effective inhibiting insulin secretion. During a 16.6 mM glucose stimulus, sequential modifications of extracellular pH (7.4-7.8-7.4) caused a dramatic decrease in insulin secretion during alkalosis and an enhancement of its release during the second 7.4 period. The installment and remotion of the inhibition followed almost immediately the changes in the pH of the perfusates. These findings indicate that extracellular diminution of H+ concentration produces a gradual and quickly reversible decrease upon glucose-induced insulin secretion. These characteristics suggest that the inhibitory effect may be mediated through changes in intracellular and/or transmembrane ion fluxes coupled to the variations in H+ concentration.     

Salicylate reduces serum insulin concentrations in the rat

Administration of sodium salicylate (50–500 mg/kg, i.p.) reduced serum insulin concentrations in nonfasted rats. This treatment also suppressed the rise in serum insulin that followed oral administration of glucose (by stomach tube) to fasted rats; this effect is only partly attributable to the blunted increase in serum glucose concentrations.     

Insulin-like growth factor I levels decrease in the development of diabetes inMacaca nigra

Members of the monkey speciesMacaca nigra spontaneously develop impairments in insulin secretion and glucose clearance, and eventually become overtly diabetic. Changes in certain metabolic signals such as clearance of glucose and insulin increment secreted in an intravenous glucose tolerance test have allowed the identification of four stages in the progression from non-diabetes to diabetes in monkeys — non-diabetic, hormonally impaired, borderline diabetic, and diabetic. Recently, another metabolic stage, hyperinsulinemic, was also identified in these animals. In recent years, other factors besides those listed above have been implicated to be correlated with the metabolic progression from a nondiabetic to a diabetic state. One of these factors, is insulin like growth factor I (IGF-I). In diabetic humans who are in poor metabolic control, and in rats with streptozotocin induced ketotic diabetes, serum levels of IGF-I are lowered by as much as 40–50% of control non-diabetics. If indeed decreased IGF-I levels are correlated with the onset of diabetes then changes in IGF-I concentrations prior to the clinically diagnosed disease state would be expected. Using serum samples collected from different animals in a colony ofMacaca nigra in a variety of metabolic states, we have found that IGF-I and insulin levels decrease in each defined metabolic state as the animals progress from nondiabetic to diabetic. Since IGF-I and insulin levels decrease in a similar fashion in the progression of this disease then this maybe indicative of the coordinate expression of these two factors.     

The effect of insulin on glucose uptake in soleus muscle during hemorrhagic shock.

Hemorrhagic shock was produced by bleeding conscious rats to a mean arterial pressure of 40 mm Hg, which was maintained for 2 h. Basal glucose uptake by isolated soleus muscle from normal rats and rats subjected to hemorrhagic shock ('shock' muscles) increased with the increase ib medium glucose concentration. Uptake values were similar in both groups of muscles. This indicates that there were no alterations in the basal glucose carrier mechanism during shock. Whereas insulin (0.1 U/ml) stimulated glucose uptake in control muscles under aerobic as well as under anaerobic conditions, it had no stimulatory effect in 'shock' muscles under either environment. Maximal stimulation of glucose uptake in 'shock' muscles was observed at an insulin concentration of 0.2 U/ml. The ability of muscle to bind insulin was not altered during shock. The present experiments indicate that insulin responsiveness to tissues is altered in shock. This could be due to alterations in the insulin sensitivity of the glucose carrier mechanism during shock.     

Effects of a high-salt diet on adipocyte glucocorticoid receptor and 11-β hydroxysteroid dehydrogenase 1 in salt-sensitive hypertensive rats

High-salt diets decrease insulin sensitivity in salt-sensitive hypertensive rats, and glucocorticoids promote adipocyte growth and may have pathophysiological roles in the metabolic syndrome. The aim of this study was to clarify the relationship between high-salt diet and the adipocyte glucocorticoid hormones in salt-sensitive hypertensive rats. Six-week-old Dahl salt-sensitive (DS) hypertensive rats and salt-resistant (DR) rats were fed a high-salt diet or a normal-salt diet for 4 weeks. Fasting blood glucose (FBG), serum adiponectin, plasma insulin, and corticosterone in plasma and in visceral adipose tissues, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) activities in adipose tissues and glucose uptake in isolated muscle were measured. Animals underwent an oral glucose tolerance test (OGTT). The expression of mRNA for glucocorticoid receptor (GR), 11β-HSD1 and tumor necrosis factor-α (TNF-α) in adipose tissues were measured using a real-time PCR. A high-salt diet did not influence FBG; however, decreased 2-deoxy glucose uptake and plasma insulin during OGTT in DS rats. The high-salt diet increased significantly adipose tissue corticosterone concentration and 11β-HSD1 activities, gene expression for GR, 11β-HSD1 and TNF-α in adipose tissues in DS rats compared with DR rats (p < 0.05). The high-salt diet did not influence plasma corticosterone and serum adiponectin concentration in DS and DR rats. These results suggest that changes in GR and 11β-HSD1 in adipose tissue may contribute to insulin sensitivity in salt-sensitive hypertensive rats.