This study assessed the effect of physical training on the low Michaelis constant cyclic AMP phosphodiesterase (low Km PDE) activity in heart ventricular tissue and three different skeletal muscle tissues of normal and diabetic rats. Rats were rendered diabetic with streptozotocin (45 mg/kg i.v.) and either kept sedentary (SD, n=16) or submitted to a progressive 10-week treadmill running program (TD, n=17). Two groups of nondiabetic rats served as trained (TC, n=17) and sedentary controls (SC, n=15). The activity of NAD-linked isocitrate dehydrogenase was significantly increased (p < 0.001) in the gastrocnemius muscle of trained animals, confirming that they were adequately trained. Plasma glucose levels were elevated in SD rats (18.8 ± 1.7 mmol/l) compared to those in SC rats (7.7 ± 0.2 mmol/l ; mean ± standard error of the mean [SEM], p < 0.001). These levels were partially normalized following training (12.7 ± 1.7 pmol/l; p < 0.01 vs. SD rats). Plasma insulin levels were significantly reduced in TC rats (223 ± 16 pmol/l) compared with those in SC rats (306 ± 13 pmol/l; p < 0.01). Similarly, the levels in SC rats were significantly different when compared with SD rats (155 ± 15 pmol/l; p < 0.01). In TD rats, plasma insulin levels (156 ± 14 pmol/l) were similar to those of SD rats. This suggests that mild diabetes mellitus in the rat can be improved by endurance training and that improved glycemic control may be mediated by an increase in insulin sensitivity. The low Km PDE activity in the membranes prepared from the four different muscle tissues was not modified by diabetes. Similarly, physical training in normal and diabetic rats did not induce any significant changes in the low Km PDE activity in any of the tissues tested. This suggests that improvements in myocardial contractile function and in glucose homeostasis, as seen in diabetic rats submitted to endurance training, are not associated with changes in PDE.

We investigated the effects of treatment with tempol (an antioxidant) on vascular and metabolic dysfunction induced by a high-fat high-sucrose (HFHS) diet. Rats were randomized to receive an HFHS or chow diet with or without tempol treatment (1.5 mmol·(kg body mass) −1 ·day −1 ) for 4 weeks. Blood pressure, heart rate, and blood flow were measured in the rats by using intravascular catheters and Doppler flow probes. Insulin sensitivity and vascular responses to insulin were assessed during a euglycemic–hyperinsulinemic clamp. In-vitro studies were performed to evaluate vascular reactivity and endothelial and inducible nitric oxide synthase (eNOS; iNOS) expression in vascular and muscle tissues. Endothelin, nitrotyrosine, and NAD(P)H oxidase expressions were determined in vascular tissues, and glucose transport activity and glucose transporter 4 (GLUT4) expression were examined in muscles. Tempol treatment was found to prevent alterations in insulin sensitivity, glucose transport activity, GLUT4 expression, and vascular reactivity, and to prevent increases in plasma insulin, blood pressure, and heart rate noted in the untreated HFHS-fed rats. These were associated with increased levels of eNOS expression in vascular and muscle tissues, but reductions in nitrotyrosine, endothelin, NAD(P)H oxidase, and iNOS expressions. Therefore, oxidative stress induced by a relatively short-term HFHS diet could contribute to the early development of vascular and metabolic abnormalities in rats.

BACKGROUND:New cardiovascular disease (CVD) risk factors are being recognized and suggested to be included in CVD risk stratification. High-sensitivity C-reactive protein (hs-CRP) and the metabolic syndrome (MetS) are among these risk factors. However, CVD risk classification may be divergent when using different approaches.OBJECTIVES:To compare differences in CVD risk estimation using the Framingham risk score (FRS), hs-CRP and the presence of the MetS in a group of 109 postmenopausal women in primary CVD prevention.METHODS:The FRS and presence of the MetS were determined. CVD risk was evaluated with a cardiovascular point scoring system based on Framingham covariables and hs-CRP values (Women's Health Study [WHS] model). The estimated CVD risks based on hs-CRP levels and the WHS model were compared with the FRS.RESULTS:Using the FRS, 99% of women (n=108) were determined to have a low CVD risk. The MetS was identified in 39.4% (n=43) of the women. When hs-CRP was used alone to estimate CVD risk, 37.6% (n=41) of women were classified as being at low, 33.9% (n=37) at moderate and 28.4% (n=31) at high CVD risk. With the WHS model, 83.5% (n=91), 14.7% (n=16) and 1.8 % (n=2) of women were classified as being at low, moderate and high CVD risk, respectively.CONCLUSIONS:A substantial number of postmenopausal women showing evidence of the MetS were not identified by the FRS, even though women with the MetS are at higher risk of CVD. Estimation of risk by hs-CRP is significantly divergent when using conventional hs-CRP cutoff values compared with an integrated use in the WHS model.

This study was designed to examine the effects of a high-fat, high-sucrose (HFHS) diet on vascular and metabolic actions of insulin. Male rats were randomized to receive an HFHS or regular chow diet for 4 wk. In a first series of experiments, the rats had pulsed Doppler flow probes and intravascular catheters implanted to measure blood pressure, heart rate, and regional blood flows. Insulin sensitivity and vascular responses to insulin were assessed during a euglycemic hyperinsulinemic clamp performed in conscious rats. In a second series of experiments, new groups of rats were used to examine skeletal muscle glucose transport activity and to determine in vitro vascular reactivity, endothelial nitric oxide synthase (eNOS) protein expression in muscle and vascular tissues and endothelin content, nitrotyrosine formation, and NAD(P)H oxidase protein expression in vascular tissues. The HFHS-fed rats displayed insulin resistance, hyperinsulinemia, hypertriglyceridemia, hyperlipidemia, elevated blood pressure, and impaired insulin-mediated renal and skeletal muscle vasodilator responses. A reduction in endothelium-dependent vasorelaxation, accompanied by a decreased eNOS protein expression in muscles and blood vessel endothelium, and increased vascular endothelin-1 protein content were also noted in HFHS-fed rats compared with control rats. Furthermore, the HFHS diet induced a reduced insulin-stimulated glucose transport activity in muscles and increased levels of NAD(P)H oxidase protein and nitrotyrosine formation in vascular tissues. These findings support the importance of eNOS protein in linking metabolic and vascular disease and indicate the ability of a Westernized diet to induce endothelial dysfunction and to alter metabolic and vascular homeostasis.

The aim of the study was to examine how body fat distribution variables were associated with metabolic parameters in a sample of 113 postmenopausal women not receiving hormone therapy (56.9 +/- 4.4 years, 28.4 +/- 5.1 kg/m(2)). Body fat distribution variables (visceral adipose tissue [AT], subcutaneous AT, and total midthigh AT) were measured using computed tomography; body fat mass was assessed by hydrostatic weighing; insulin sensitivity was determined with the euglycemic-hyperinsulinemic clamp; fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) concentrations were measured by a 75-g oral glucose load; and (high-sensitivity) C-reactive protein (hs-CRP) was measured using a highly sensitive assay. After controlling for fat mass, visceral AT was positively associated with plasma triglyceride, hs-CRP, FPG, and 2hPG, and negatively associated with high-density lipoprotein cholesterol (HDL-C) and insulin sensitivity. Total midthigh AT was negatively associated with apolipoprotein B, FPG, and 2hPG, and positively associated with insulin sensitivity. Stepwise multiple regression analyses including abdominal visceral AT, subcutaneous AT and total midthigh AT as independent variables showed that abdominal visceral AT best predicted the variance in plasma triglyceride, HDL-C, low-density lipoprotein peak particle size, hs-CRP, FPG, 2hPG, and insulin sensitivity. Abdominal subcutaneous AT was a significant predictor of only insulin sensitivity, whereas total midthigh AT predicted HDL-C, low-density lipoprotein peak particle size, and apolipoprotein B. These multivariate analyses also indicated that total midthigh AT was favorably related to these outcomes, whereas abdominal visceral AT and subcutaneous AT were unfavorably related. These results confirmed that abdominal visceral fat is a critical correlate of metabolic parameters in postmenopausal women. In addition, a higher proportion of AT located in the total midthigh depot is associated with a favorable metabolic profile.

Associations between eating behaviours and dietary variables have not been thoroughly investigated in healthy postmenopausal women in a real-life uncontrolled context. To investigate how eating behaviours (cognitive dietary restraint, disinhibition and susceptibility to hunger) were associated with food and drink consumption, energy density and meal pattern in 112 healthy postmenopausal women (age 56·8 (sd 4·4) years) not on hormonal therapy. Women completed a 3 d weighed food record and filled out the Three-Factor Eating Questionnaire. The sample was divided according to the median of the distribution of cognitive dietary restraint and disinhibition (9 and 6 respectively). Both subgroups of women with high restraint level (presenting either high or low disinhibition) consumed a diet with a lower energy density than subgroups of women with lower restraint level. Women with high restraint–low disinhibition had a lower consumption of red meat and processed meat and a lower consumption of diet soft drinks than women with low restraint–high disinhibition. They were also characterised by a higher intake of whole grains than women with high restraint–high disinhibition and than women with lower restraint level (with either high or low disinhibition). Women with high restraint–high disinhibition levels showed differences in dietary variables when compared with subgroups of women with lower restraint level, namely for refined grains and diet soft drinks. We conclude that in healthy postmenopausal women, dietary consumption of specific food and drink may be related to particular eating behaviours. Women with high restraint and low disinhibition levels generally showed the most healthy dietary pattern.

This study compares indices of insulin sensitivity derived from fasting and oral glucose tolerance test (OGTT) glucose and insulin measurements, with respect to the reference measure (M/I), obtained from the euglycemic-hyperinsulinemic clamp, in postmenopausal women with varying glucose tolerance status. Fasting plasma insulin index, homeostasis model assessment index, and OGTT-derived indices (insulin 120-minute, Matsuda, metabolic clearance rate [MCR] of glucose, insulin sensitivity [ISI], and Cederholm indices) were calculated and compared with the M/I value in 112 postmenopausal women. All indices examined were significantly correlated with M/I (0.28 ≤ r2 ≤ 0.56). Association studies revealed that on average, 48% of women were grouped in the same tertile of insulin sensitivity when using M/I and fasting plasma insulin index, and 54% when using M/I and insulin 120-minute index. However, concordance with M/I tertiles were 57%, 58%, 64%, 64%, and 68% for homeostasis model assessment, Matsuda, MCR, ISI, and Cederholm indices, respectively. Finally, correlation coefficients between M/I and insulin sensitivity indices were generally lower in women with normal glucose tolerance compared with women with impaired glucose tolerance or type 2 diabetes mellitus. These results suggest that in postmenopausal women, surrogate indices of insulin sensitivity obtained from OGTT data and incorporating a measurement of body weight or body mass index) (Cederholm, ISI, and MCR indices) appear to be superior to those without OGTT data or body weight-body mass index measurements and, therefore, could offer a better estimate of insulin sensitivity, allowing an improved clinical evaluation of this population at higher risk of cardiovascular disease and type 2 diabetes mellitus.

Background Information on the extent to which acute exercise reduces blood glucose levels (BGL) in type 2 diabetes is lacking. For this reason, the effects of exercise initiated at different preexercise BGL were assessed in men with type 2 diabetes both in the fasted (FS) and the postprandial states (PS).Design and methods Forty-three men with type 2 diabetes, 12 on diet alone and 31 on hypoglycaemic agents, completed a total of 1555 exercise sessions performed in the FS and 0-1, 1-2, 2-3, 3-4, 4-5, and 5-8 h in the PS. Capillary BGL were measured before and immediately after a 1 h standardized aerobic exercise session on an ergocycle at 60% of Vo(2) peak.Results In the FS, there was an increase in postexercise BGL of 27 +/- 21% (mean +/- SD; P<0.001) when preexercise BGL was <= 6mmol/l, no change when preexercise 13GL were between 6 and 8mmol/l, and a significant decrease of 12 +/- 13% when preexercise BGLwere >8mmol/I (P<0.001). In the PS, most exercise sessions were associated with significant decreases in BGL ranging between 18 +/- 17 and 50 +/- 12% (P<0.001), depending on the time interval between meals and the onset of exercise. Regarding the metabolic PS, the decline in 13GL was most pronounced with high preexercise BGL.Conclusions Our observations not only demonstrate that it was safe for middle-aged obese men with type 2 diabetes to exercise in the FS, but also show that the decrease in BGL during aerobic exercise was largely dependent on preexercise BGL. Eur J Cardiovasc Prev Rehabil 14:831-836 (c) 2007.

This study was designed to examine whether the training-induced improvement in the plasma concentration of ketone bodies in experimental diabetes mellitus could be explained by changes in the activity of the hepatic ketone body synthesis pathway and/or the plasma free fatty acid levels. Diabetes mellitus was induced by an intravenous injection of streptozotocin (50 mg/kg), and training was carried out on a treadmill. The plasma concentration of beta-hydroxybutyric acid was increased (P < 0.001) in sedentary diabetic rats, and this was partly reversed by training (P < 0.001). The plasma concentration of free fatty acids was increased (P < 0.001) in sedentary diabetic rats, and this was reversed to normal by training (P < 0.001). Diabetes was also associated with an increased activity of the hepatic ketone body synthesis pathway. When the data are expressed as per total liver, physical training decreased the activity of the hepatic ketone body synthesis pathway by 18% in nondiabetic rats (P < 0.05) and by 22% in diabetic rats (P < 0.01), the activity present in trained diabetic rats being not statistically different from that of sedentary control rats. These data suggest that the beneficial effects of physical training on the plasma beta-hydroxybutyric acid levels in the diabetic state are probably explained in part by a decrease in the activity of the hepatic ketone body synthesis pathway and in part by a decrease in plasma free fatty acid levels.

This study was designed to investigate the effects of a sucrose diet on vascular and metabolic actions of insulin in spontaneously hypertensive rats (SHR). Male SHR were randomized to receive a sucrose or regular chow diet for 4 wk. Age-matched, chow-fed Wistar-Kyoto (WKY) rats were used as normotensive control. In a first series of experiments, the three groups of rats had pulsed Doppler flow probes and intravascular catheters implanted to determine blood pressure, heart rate, and blood flows. Insulin sensitivity was assessed during a euglycemic hyperinsulinemic clamp performed in conscious rats. In a second series of experiments, new groups of rats were used to examine glucose transport activity in isolated muscles and to determine endothelial nitric oxide synthase (eNOS) protein expression in muscles and endothelin content in vascular tissues. Sucrose feeding was shown to markedly enhance the pressor response to insulin and its hindquarter vasoconstrictor effect when compared with chow-fed SHR. A reduction in eNOS protein content in muscle, but no change in vascular endothelin-1 protein, was noted in sucrose-fed SHR when compared with WKY rats, but these changes were not different from those noted in chow-fed SHR. Similar reductions in insulin-stimulated glucose transport were observed in soleus muscles from both groups of SHR when compared with WKY rats. In extensor digitorum longus muscles, a significant reduction in insulin-stimulated glucose transport was only seen in sucrose-fed rats when compared with the other two groups. Environmental factors, that is, high intake of simple sugars, could possibly potentiate the genetic predisposition in SHR to endothelial dysfunction and insulin resistance.

Oxidized low-density lipoproteins (ox-LDL) play a significant role in the development of atherosclerosis.Objective: To investigate the relation between circulating ox-LDL and components of the metabolic syndrome (NIS) in a sample of 124 postmenopausal women with varying glucose tolerance status.Methods: This cross-sectional study included postmenopausal women not using hormone therapy. Ox-LDL concentrations were measured in plasma by a monoclonal antibody (mAb-4E6) based competition ELISA. LDL peak particle diameter (LDL-PPD) was measured by nondenaturating polyacrylamide gradient gel electrophoresis (PAGGE). Presence of the NIS was determined according to the definition of the NCEP-ATPIII.Results: Circulating ox-LDL concentrations were significantly associated with some factors of the NIS such as trialyceride (r=0.48; p < 0.0001), high-density lipoprotein cholesterol (r= -0.34;p = 0.0001) and fasting plasma glucose concentrations (r= 0.21;p = 0.02). Ox-LDL concentrations were also associated with LDL cholesterol (r=0.54;p < 0.0001), total cholesterol (r=0.48;p < 0.0001), LDLapolipoprotein B (r=0.62;p < 0.0001) and LDL-PPD (r = -0.18;p < 0.05). Moreover, women with the MS had significantly higher ox-LDL concentrations (79.5 +/- 28.3 U/I) compared to women without the MS (64.2 +/- 19.9 U/I) (P < 0.05).Conclusion: Ox-LDL concentrations are associated with individual components of the MS and are significantly higher in postmenopausal women with MS compared to healthy postmenopausal women. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

This study was designed to test the glucose metabolic and vasodilator actions of insulin in rats and its relation to cholinergic system-dependent mechanisms. The first group of rats had pulsed Doppler flow probes and intravascular catheters implanted to determine blood pressure, heart rate, and regional blood flows. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp technique carried out in the absence or presence of atropine. The second group of rats was used to determine the cholinergic contribution to in vivo insulin-mediated glucose utilization in individual muscles. Glucose uptake was examined by using [(3)H]2-deoxy-D-glucose. Muscarinic cholinergic blockade was found to significantly (P = 0.002) reduce insulin sensitivity and to completely abrogate the renal (P = 0.008) and hindquarter (P = 0.02) vasodilator responses to euglycemic infusion of insulin. A significant reduction in insulin-stimulated in vivo glucose uptake was also noted in soleus (P = 0.006), quadriceps (P = 0.03), gastrocnemius (P = 0.02), and extensor digitorum longus (EDL) (P = 0.001) muscles, when insulin was infused at a rate of 4 mU . kg(-1) . min(-1), whereas at the rate of 16 mU . kg(-1) . min(-1), a significant reduction in glucose uptake was only observed in EDL (P = 0.03) and quadriceps (P = 0.01) muscles. Together, these results demonstrate a potential role for cholinergic involvement with physiological insulin actions in glucose clearance and blood flow regulation in rats.

BACKGROUND:The aim of this study was to examine the metabolic risk profile in postmenopausal women characterized by either the metabolic syndrome (MS) as defined by the World Health Organization (WHO) or the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII).METHODS:One hundred and eight postmenopausal women (56.9 +/- 4.2 years; 28.5 +/- 5.9 kg/m(2)) were examined. Each underwent an oral glucose tolerance test, an euglycemic-hyperinsulinemic clamp, an assessment of body fat distribution by computed tomography, a complete plasma lipid-lipoprotein profile, and standard measurements of inflammatory markers.RESULTS:The prevalence of the MS-WHO was 29.6% in our women. Type 2 diabetes was found in 28.1% of women with the MS-WHO. Thirty-one percent of women had the MS-ATP, from which 36.4% had type 2 diabetes. Among the 32 women identified as having MS-WHO, 25 (78.1 %) were also identified as having the MS-ATP. On the other hand, among the 34 women identified as having MS-ATP, 24 (70.0 %) also had MS-WHO (kappa = 0.60). When we subdivided our sample of women as having either isolated MS-WHO, isolated MS-ATP, or combined MS-WHO and MS-ATP, we observed a more deteriorated metabolic risk profile (higher values for visceral adipose tissue, 2-h plasma glucose, and lower HDL-cholesterol concentrations) in women characterized by isolated MS-ATP compared to women with isolated MS-WHO.CONCLUSIONS:These results suggest that, in postmenopausal women, the concordance in the identification of subjects with the MS using each of the proposed definitions is only moderate.

To investigate one potential mechanism whereby physical training improves the plasma concentration of ketone bodies in experimental diabetes mellitus, we measured the activity of 3-ketoacid CoA-transferase, the key enzyme in the peripheral utilization of ketone bodies. Diabetes was induced with streptozotocin (50 mg/kg) and training carried out on a treadmill with a progressive 10-wk program. Diabetes resulted in an increase (P < 0.001) in plasma concentration of beta-hydroxybutyric acid in sedentary rats, which was partly reversed by training (P < 0.001). Diabetes was also associated with a decreased activity of 3-ketoacid CoA-transferase in gastrocnemius muscle. When expressed per total gastrocnemius, training increased the activity of 3-ketoacid CoA-transferase by 66% in nondiabetic rats (P < 0.001) and by 150% in diabetic rats (P < 0.001), the decrease present in diabetic rats being fully reversed by training. Simple linear regression between the log of 3- ketoacid CoA-transferase activity and the log of plasma beta-hydroxybutyric acid levels showed a statistically significant (r = 0.563, P < 0.001) negative correlation. The beneficial effects of training on plasma ketone bodies in diabetic rats are probably explained, at least in part, by an increase in ketone body utilization, mediated by an increase in skeletal muscle 3-ketoacid CoA-transferase activity.

In rats, diets high in simple sugar induce insulin resistance and alter vascular reactivity. The present study was designed to evaluate the effects of 5 weeks treatment with troglitazone on insulin sensitivity, regional hemodynamics, and vascular responses to insulin in chow-fed and high-sucrose-fed rats. Male rats were randomly divided in 4 groups to receive a regular chow diet in the absence (group 1) or presence of troglitazone (0.2% in food; group 2), or a sucrose-enriched diet in the absence (group 3) or presence of troglitazone (group 4) for 5 weeks. The rats were instrumented with Doppler flow probes and intravascular catheters to determine blood pressure, heart rate, and regional blood flows. Insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp technique. Glucose transport activity was examined in isolated muscles. Sucrose feeding was found to induce insulin resistance and to impair the insulin-mediated skeletal muscle vasodilation. Treatment with troglitazone was found to increase whole-body insulin sensitivity in sucrose- and chow-fed rats, but had no effect on skeletal muscle glucose transport activity measured in isolated muscles from both dietary groups. Changes in regional hemodynamics were observed in both dietary cohorts treated with troglitazone, and the hindquarter vasoconstrictor response to insulin noted in sucrose-fed rats was abolished by the treatment. The vascular effects of troglitazone, and its insulin-related attenuating effects on contractile tone, could have contributed, in part, to improve insulin action on peripheral glucose disposal, presumably by improving blood flow distribution and glucose delivery.

WSTĘP. Celem pracy jest określenie, czy upośledzona tolerancja glukozy (IGT, impaired glucose tolerance ) odpowiada za pogorszenie profilu metabolicznego u kobiet, uwzgledniając nagromadzenie trzewnej tkanki tluszczowej, mierzone w tomografii komputerowej. MATERIAŁ I METODY. Przebadano 203 kobiety z prawidlowym wynikiem testu tolerancji glukozy (NGT, normal glucose tolerance ) oraz 46 kobiet z upośledzoną tolerancją glukozy - glikemia mierzona 2 godziny po doustnym obciązeniu 75 g glukozy - 7,8-11,1 mmol/l. WYNIKI. U kobiet z IGT stwierdzano wieksze nagromadzenie trzewnej tkanki tluszczowej oraz wyzsze stezenie glukozy na czczo w osoczu, insuliny oraz C-peptydu, a takze wyzsze stezenie cholesterolu, triglicerydow i apolipoproteiny B (apoB) oraz wiekszy stosunek cholesterolu calkowitego do cholesterolu frakcji HDL, zmniejszenie maksymalnej wielkości cząsteczek LDL, nizsze stezenie cholesterolu frakcji HDL i HDL 2 oraz wyzsze ciśnienie tetnicze (p 2 , a takze stosunku cholesterolu calkowitego do cholesterolu frakcji HDL i ciśnienia tetniczego zniknely, natomiast stezenie triglicerydow pozostawalo znamiennie wyzsze u kobiet z upośledzoną tolerancją glukozy. WNIOSKI. Nagromadzenie trzewnej tkanki tluszczowej jest glownym czynnikiem powodującym pogorszenie wielu parametrow metabolicznych u kobiet z IGT, z wyjątkiem stezenia triglicerydow, ktore roznilo sie znamiennie pomiedzy kobietami z NGT a kobietami z IGT, nawet po skorygowaniu w odniesieniu do trzewnej tkanki tluszczowej.