Biomedical subjects

P Nuutila

Publications and source records attributed to P Nuutila.

At least 19 recordsLinked to original sources

PubMed2006

Exercise restores skeletal muscle glucose delivery but not insulin-mediated glucose transport and phosphorylation in obese subjects.

CONTEXT/OBJECTIVE: Insulin resistance in obese subjects results in the impaired disposal of glucose by skeletal muscle. The current study examined the effects of insulin and/or exercise on glucose transport and phosphorylation in skeletal muscle and the influence of obesity on these processes. SUBJECTS/METHODS: Seven obese and 12 lean men underwent positron emission tomography with 2-deoxy-2-[(18)F]fluoro-d-glucose in resting and isometrically exercising skeletal muscle during normoglycemic hyperinsulinemia. Data were analyzed by two-tissue compartmental modeling. Perfusion and oxidative capacity were measured during insulin stimulation by [15O]H2O and [15O]O2. RESULTS: Exercise increased glucose fractional uptake (K), inward transport rate (K(1)), and the k(3) parameter, combining transport and intracellular phosphorylation, in lean and obese subjects. In each group, there was no statistically significant difference between plasma flow and K(1). At rest, a significant defect in K(1) (P = 0.0016), k(3) (P = 0.016), and K (P = 0.022) was found in obese subjects. Exercise restored K(1), improved but did not normalize K (P = 0.03 vs. lean), and did not ameliorate the more than 60% relative impairment in k(3) in obese individuals (P = 0.002 vs. lean). The glucose oxidative potential tended to be reduced by obesity. CONCLUSIONS/INTERPRETATION: The study indicates that exercise restores the impairment in insulin-mediated skeletal muscle perfusion and glucose delivery associated with obesity but does not normalize the defect involving the proximal steps regulating glucose disposal in obese individuals. Our data support the use of 2-deoxy-2-[18F]fluoro-d-glucose-positron emission tomography in the dissection between substrate supply and intrinsic tissue metabolism.

Adult↗

PubMed2006

The effect of 12-month enzyme replacement therapy on myocardial perfusion in patients with Fabry disease.

Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder secondary to deficient alpha-galactosidase A activity which leads to the widespread accumulation of globotriaosylceramide (Gb(3)) and related glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. We have recently shown that the myocardial perfusion reserve of Fabry patients is significantly decreased. Thus, in the present study we investigated, whether it can be improved with enzyme replacement therapy (ERT). Ten patients (7 male, 3 female; mean age 34, range 19-49 years) with confirmed Fabry disease were approved for this uncontrolled, open-label study. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and radiowater. Myocardial perfusion reserve was calculated as the ratio between maximal and resting perfusion. Perfusion measurements were performed before and after 6 and 12 months of ERT by recombinant human alpha-galactosidase A (Fabrazyme, Genzyme). Plasma Gb(3) concentration decreased significantly and the patients reported that they felt better and suffered less pain after the ERT. However, neither resting or dipyridamole-stimulated myocardial perfusion nor myocardial perfusion reserve changed during the ERT. Pretreatment relative wall thickness correlated negatively with posttreatment changes in flow reserve (r = -0.76, p = 0.05) and positively with posttreatment changes in minimal coronary resistance (r = 0.80, p = 0.03). This study shows that 12 months of ERT does not improve myocardial perfusion reserve, although the plasma Gb(3) concentration decreases. However, individual variation in the response to therapy was large and the results suggest that the success of the therapy may depend on the degree of cardiac hypertrophy.

Adult↗

PubMed2006

Short-term changes in inflammatory response protein (hsCRP) do not parallel with changes in coronary vasoreactivity in obese men.

AIM: Obese subjects are characterized by increased high-sensitivity C-reactive protein (hsCRP) and coronary vascular resistance. Clucocorticoids suppress inflammation, a possible cardioprotective effect. We tested the short-term anti-inflammatory effect of dexamethasone (dx) on these parameters in obese subjects. METHODS: Coronary vascular resistance was quantitated basally and during adenosine infusion with or without simultaneous euglycemic hyperinsulinemic clamp (insulin infusion rate of 1 mU/kg/min) in 11 obese and 19 age-matched nonobese males using positron emission tomography and (15)O-water. Each subject was studied both with and without previous dx treatment for 2 days (2 mg/day). RESULTS: Before dx treatment, hsCRP concentration was significantly higher in obese than in nonobese subjects (1.55+/-1.73 vs 0.32+/-0.32 mg/l, P = 0.005). In addition, coronary vascular resistances were higher (P < 0.05) in obese than in nonobese subjects at baseline (139+/-36 vs 117+/-22) and during adenosine infusion without (32+/-7 vs 26+/-7) or with simultaneous clamp (26+/-8 vs 21+/-5 mmHg min g/ ml). Dx treatment decreased significantly hsCRP concentration in obese but not in nonobese subjects, leading to similar hsCRP concentrations between the groups (0.45+/-0.43 vs 0.26+/-0.42 mg/l, respectively, P = 0.3). Dx had no effect on coronary vascular resistances (NS). CONCLUSIONS: Obese subjects are characterized by high hsCRP, which can be normalized by dx. However, despite this, coronary vascular resistances did not decrease in obese subjects. Short-term changes in inflammatory response protein appear not to parallel with changes in coronary vasoreactivity in obese men.

Adenosine↗

PubMed2006

Effects of exhaustive stretch-shortening cycle exercise on muscle blood flow during exercise.

AIM: The influence of exhaustive stretch-shortening cycle exercise (SSC) on skeletal muscle blood flow (BF) during exercise is currently unknown. METHODS: Quadriceps femoris (QF) BF was measured in eight healthy men using positron emission tomography before and 3 days after exhaustive SSC exercise. The SSC protocol consisted of maximal and submaximal drop jumps with one leg. Needle biopsies of the vastus lateralis muscles were taken immediately and 2 days after SSC for muscle endothelial nitric oxide synthase (eNOS) and interleukin-1-beta (IL-1beta) mRNA level determinations. RESULTS: All subjects reported subjective muscle soreness after SSC (P < 0.001), which was well in line with a decrease in maximal isometric contraction force (MVC) and increase in serum creatine kinase activity (CK) (P = 0.018). After SSC muscle BF was 25% higher in entire QF (P = 0.043) and in its deep and superficial muscle regions, whereas oxygen uptake remained unchanged (P = 0.893). Muscle biopsies revealed increased IL-1beta (30 min: 152 +/- 75%, P = 0.012 and 2 days: 108 +/- 203%, P = 0.036) but decreased or unchanged eNOS (30 min; -21 +/- 57%, P = 0.050 and 2 days: +101 +/- 204%, P = 0.779) mRNA levels after SSC. CONCLUSION: It was concluded that fatiguing SSC exercise induces increased muscle BF during exercise, which is likely to be associated with pro-inflammatory processes in the exercised muscle.

Adult↗

PubMed2005

Impaired myocardial perfusion reserve but preserved peripheral endothelial function in patients with Fabry disease.

Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder due to deficient alpha-galactosidase A activity, which leads to accumulation of glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. The effect of this accumulation on peripheral and cardiac vascular function is poorly known. We studied 15 Fabry patients (mean age 35 years and mean BMI 24.8 kg/m2) and 30 age- and BMI-matched healthy controls to examine whether myocardial perfusion reserve and peripheral artery endothelial function are altered. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and H2(15)O. Myocardial blood flow reserve was calculated as the ratio between the dipyridamole-induced maximal blood flow and resting blood flow. Peripheral artery endothelial function was assessed by measuring the brachial artery flow-mediated dilatation using ultrasound at rest and during reactive hyperaemia. The myocardial perfusion reserve was significantly lower in Fabry patients than in controls (3.3+/-1.2 vs 4.4+/-1.6, p=0.02), while the brachial artery flow-mediated dilatation was similar (5.9%+/-3.9% vs 4.5%+/-3.6%, p=0.27). Thus, inFabry disease, myocardial perfusion reserve is reduced while the peripheral artery endothelial function is preserved.

Adult↗

PubMed2005

In vivo measurements of glucose uptake in human Achilles tendon during different exercise intensities.

Muscular contraction and loading of adjacent tendons has been demonstrated to cause increased blood flow and metabolic activity in the peritendinous region. However, it is poorly known to what extent the human tendon itself takes up glucose during exercise. Thus, the purpose of this study was to measure tendon glucose uptake with increasing exercise intensity and to compare it to muscle glucose uptake at the same intensities. Eight young men were examined on three separate days during which they performed 35 min of cycling at 30, 55 and 75 % of VO2max, respectively. Glucose uptake was measured directly by positron emission tomography (PET) with 2-[ (18)F]fluoro-2-deoxyglucose ([18F]FDG). [18F]FDG was injected after 10 min of exercise that was continued for a further 25 min after the injection. PET scanning of the thigh and Achilles region was performed after the exercise. Glucose uptake of the Achilles tendon (AT) remained unchanged (7.1 +/- 1.5, 6.6 +/- 1.1, and 6.0 +/- 1.1 micromol.kg(-1).min(-1)) with the increasing workload, although the glucose uptake in m. quadriceps femoris simultaneously clearly increased (48 +/- 35, 120 +/- 35, and 152 +/- 74 micromol.kg(-1).min(-1), p < 0.05). In conclusion, the AT takes up glucose during exercise but in significantly smaller amounts than the skeletal muscle does. Furthermore, glucose uptake in the AT is not increased with the increasing exercise intensity. This may be partly explained by the cycle ergometry exercise used in the present study, which probably causes only a little increase in strain to the AT with increasing exercise intensity.

Achilles Tendon↗

PubMed2005

Role of skeletal muscle-fibre type in regulation of glucose metabolism in middle-aged subjects with impaired glucose tolerance during a long-term exercise and dietary intervention.

AIM: The aim of this study was to investigate the role of skeletal muscle fibre type in the regulation of glucose metabolism in middle-aged obese subjects with impaired glucose tolerance (IGT) during a 2-year exercise and dietary intervention. METHODS: Muscle biopsies (musculus vastus lateralis) were taken from 22 subjects belonging to the intervention group of the Finnish Diabetes Prevention Study [1]. According to their myosin heavy chain (MHC) profile at the baseline, the subjects were divided into two groups: IGT(slow) (n=10) with a high proportion of MHC I isoforms and IGT(fast) (n=12) with a high proportion of MHC II isoforms in the vastus lateralis muscle. The intervention consisted of dietary counselling, strength and power training and/or aerobic exercise. The amount of exercise was the same in both groups; the exercise frequency was 5.1+/-2.7 h/week in the IGT(slow) and 5.1+/-2.8 h/week in the IGT(fast) group. RESULTS: Fasting glucose (p<0.05), 2-h glucose (p<0.05), fasting insulin (p<0.05), haemoglobin A1c (HbA(1c)) (p<0.01) and insulin resistance (p<0.05) [homeostasis model assessment for insulin resistance (HOMA-IR)] decreased in the IGT(fast) group, whereas only the 2-h glucose and HbA(1c) concentrations decreased in the IGT(slow) group. The amount of the glycogen synthase kinase-3-alphabeta (GSK-3-alphabeta) decreased in the IGT(fast) group (p<0.05). Exercise training increased the lactate dehydrogenase (LDH) (p<0.01), LDH-1 (p<0.05) and citrate synthase (CS) (p<0.05) activities in the vastus lateralis muscle in the IGT(slow) group, but only the CS activity (p<0.05) in the IGT(fast) group. CONCLUSIONS: The glucose metabolism improved both in the IGT(slow) and IGT(fast) group during the 2-year exercise and dietary intervention. The change was more prominent in the IGT(fast) group than in the IGT(slow) group, associated with the decrease of the GSK-alphabeta protein expression in skeletal muscle. The exercise training improved both glycolytic and oxidative capacity in the vastus lateralis muscle. The glycolytic capacity improved in the IGT(slow) group and the oxidative capacity in both groups.

Adult↗

PubMed2005

Lifetime glycaemic exposure predicts reduced coronary vasoreactivity in Type 1 diabetic subjects.

AIMS: Subjects with Type 1 diabetes have impaired coronary vasoreactivity but the independent role of glycaemic control on myocardial perfusion is less clear. We examined the effect of lifetime glycaemic exposure on coronary vasoreactivity in 43 otherwise healthy Type 1 diabetic subjects. METHODS: Myocardial blood flow was calculated basally and during pharmacologically induced hyperaemia in the fasting state and during euglycaemic hyperinsulinaemic clamp (at an insulin infusion rate of 1 mU/kg per min for 60 min) using positron emission tomography and (15)O-water. Glycaemic exposure was estimated as glycosylated haemoglobin A(1c) (HbA(1c)) months. RESULTS: Hyperaemic myocardial blood flow was inversely associated with log HbA(1c) months in the fasting state (r = -0.72, P < 0.01) and during clamp (r = -0.35, P < 0.05). These correlations remained significant after adjustment for lipid values, blood pressures, sex, smoking, body mass index (BMI) and age (r = -0.70, P < 0.05 and r = -0.35, P < 0.05, respectively). No significant correlation was detected between hyperaemic flow and HbA(1c) or plasma glucose values measured immediately preceding the PET study. CONCLUSIONS: The present study demonstrates that the lifetime glycaemic exposure appears to be a better predictor of reduced coronary vasoreactivity than recent glycaemic control in Type 1 diabetic subjects. Reduced coronary vasoreactivity in diabetic subjects with poor glycaemic control and/or long duration of diabetes may represent an early precursor of coronary artery disease.

Adult↗

PubMed2004

High-sensitivity C-reactive protein and impaired coronary vasoreactivity in young men with uncomplicated type 1 diabetes.

AIMS/HYPOTHESIS: Elevated high-sensitivity C-reactive protein (hsCRP) concentrations indicate increased risk of future coronary events. The association between hsCRP and coronary vasoreactivity has not yet been examined in type 1 diabetic subjects. METHODS: We studied 18 young men who were non-smokers and who had uncomplicated type 1 diabetes. The diabetic subjects were divided into two groups, according to their median hsCRP concentration, as follows: (i) subjects with slightly elevated hsCRP (median 0.76 mg/l, range 0.47-4.73 mg/l, n=8); and (ii) subjects with low hsCRP (median 0.32 mg/l, range 0.11-0.35 mg/l, n=10). In addition we investigated 22 non-diabetic age-matched subjects (hsCRP: median 0.42 mg/l, range 0.11-1.31 mg/l). Resting myocardial blood flow and hyperaemic adenosine-stimulated flow during euglycaemic-hyperinsulinaemic clamp were determined using positron emission tomography and oxygen-(15)-labelled water. RESULTS: Diabetic subjects with slightly elevated hsCRP had significantly higher hsCRP concentrations than non-diabetic subjects (p=0.008). Resting myocardial blood flow was similar (NS) in diabetic subjects with slightly elevated hsCRP (0.79+/-0.19 ml.g(-1).min(-1)) or low hsCRP (0.81+/-0.15 ml.g(-1).min(-1)) and non-diabetic subjects (0.80+/-0.19 ml.g(-1).min(-1)). Adenosine infusion induced a significant increase in blood flow in all study subjects (p<0.001) but was blunted in diabetic subjects with slightly elevated hsCRP (3.42+/-0.61 ml.g(-1).min(-1)) when compared with diabetic subjects with low hsCRP (5.08+/-1.65 ml.g(-1).min(-1), p=0.02) or non-diabetic subjects (4.51+/-1.36 ml.g(-1).min(-1), p=0.04). Adenosine-stimulated flow was inversely correlated with hsCRP concentrations in all diabetic subjects (r=-0.70, p=0.001). CONCLUSIONS/INTERPRETATION: In young subjects with uncomplicated type 1 diabetes, even slightly elevated hsCRP concentrations are associated with reduced coronary vasoreactivity.

Adult↗

PubMed2004

Non-esterified fatty acids impair insulin-mediated glucose uptake and disposition in the liver.

AIMS/HYPOTHESIS: We investigated the effect of elevated circulating NEFA on insulin-mediated hepatic glucose uptake (HGU) and whole-body glucose disposal (M) in eight healthy male subjects. METHODS: Studies were performed using positron emission tomography (PET) and [(18)F]-2-fluoro-2-deoxyglucose ([(18)F]FDG) during euglycaemic hyperinsulinaemia (0-120 min) and an Intralipid/heparin infusion (IL/Hep; -90-120 min). On a different day, similar measurements were taken during euglycaemic hyperinsulinaemia and saline infusion (SAL). Graphical and compartmental analyses were used to model liver data. RESULTS: Circulating NEFA increased approximately three-fold during IL/Hep, and declined by 81+/-7% in the SAL study ( p</=0.01). Both M (-28+/-7%) and HGU (-25+/-9%) were significantly lowered by NEFA elevation ( p=0.004 and p=0.035 respectively). In the whole data set, the decreases in M and HGU were positively correlated ( r=0.78, p=0.038). No evidence of [(18)F]FDG outflow was detected during the scanning time. HGU was correlated with the phosphorylation rate parameter ( r=0.71, p=0.003) as derived by compartmental modelling. CONCLUSIONS/INTERPRETATION: In healthy men, NEFA impair insulin-mediated HGU and whole-body glucose uptake to a similar extent. Our data suggest that multiple intracellular NEFA targets may concur to down-regulate glucose uptake by the liver.

Adult↗

PubMed2004

Diabetic background retinopathy is associated with impaired coronary vasoreactivity in people with Type 1 diabetes.

AIMS/HYPOTHESIS: We examined whether diabetic background retinopathy is associated with reduced coronary vasoreactivity in people with Type 1 diabetes. METHODS: A total of 21 men with Type 1 diabetes were investigated, including 9 men with background retinopathy and 12 men without retinopathy. In addition, 12 non-diabetic, age-matched subjects were studied. All subjects were non-smokers, otherwise healthy and had no other diabetic complications. Resting myocardial blood flow and hyperaemic dipyridamole-stimulated flow (dipyridamole, 0.56 mg/kg during a 4-min period), a measure of coronary vasoreactivity, were measured during euglycaemic hyperinsulinaemic clamp (1 mU x kg(-1) x min(-1)) using positron emission tomography and oxygen-15-labelled water. RESULTS: Resting myocardial blood flow (0.82 +/- 0.13 vs 0.96 +/- 0.23 vs 0.88 +/- 0.25 ml x g(-1) x min(-1), with vs without retinopathy vs non-diabetic subjects) and coronary vascular resistance (111.2 +/- 23.4 vs 95.5 +/- 15.8 vs 101.9 +/- 31.5 mmHg x min x g x ml(-1) respectively) were not significantly different between the groups. Dipyridamole infusion induced an increase in blood flow and a decrease in coronary vascular resistance in all study subjects (p<0.001). However, dipyridamole-stimulated flow and coronary vascular resistance were blunted in diabetic patients with retinopathy (2.9 +/- 0.9 ml x g(-1) x min(-1) and 34.1 +/- 11.3 mmHg x min x g x ml(-1)) when compared to diabetic patients without retinopathy (4.0 +/- 1.3 ml x g(-1) x min(-1), p=0.04 and 24.6 +/- 7.5 mmHg x min x g x ml(-1), p=0.03) or non-diabetic subjects (4.5 +/- 1.4 ml x g(-1) x min(-1) p=0.008 and 22.2 +/- 8.7 mmHg x min x g x ml(-1), p=0.01). Myocardial flow reserve was impaired in diabetic patients with retinopathy (3.6 +/- 1.0) when compared to non-diabetic subjects (5.3 +/- 1.9, p=0.02) but not significantly reduced when compared to diabetic patients without retinopathy (4.2 +/- 1.4, p=0.2). CONCLUSIONS/INTERPRETATION: Diabetic background retinopathy appears to be associated with impaired coronary vasoreactivity in young people with Type 1 diabetes.

Adult↗

PubMed2004

Enhancement of insulin-stimulated myocardial glucose uptake in patients with Type 2 diabetes treated with rosiglitazone.

AIMS: Peroxisome proliferator-activated receptor gamma (PPARgamma) activators have recently been identified as regulators of cellular proliferation, inflammatory responses and lipid and glucose metabolism. These agents prevent coronary arteriosclerosis and improve left ventricular remodelling and function in heart failure after myocardial infarction. Improvement in myocardial metabolic state may be one of the mechanisms behind these findings. The aim of this study was to investigate the effects of rosiglitazone on myocardial glucose uptake in patients with Type 2 diabetes. Placebo and metformin were used as control treatments. METHODS: Forty-four patients were randomized to treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.) or placebo in a 26-week double-blinded trial. Myocardial glucose uptake was measured using [(18)F]-2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and positron emission tomography (PET) during euglycaemic hyperinsulinaemia before and after the treatment. RESULTS: Rosiglitazone increased insulin-stimulated myocardial glucose uptake by 38% (from 38.7 +/- 3.4 to 53.3 +/- 3.6 micromol 100 g(-1) min(-1), P = 0.004) and whole body glucose uptake by 36% (P = 0.01), while metformin treatment had no significant effect on myocardial (40.5 +/- 3.5 vs. 36.6 +/- 5.2, NS) or whole body glucose uptake. Myocardial work as determined by the rate-pressure-product was similar between the groups. Neither treatment had any significant effect on fasting serum free fatty acids (FFA) but the FFA levels during hyperinsulinaemia were more suppressed in the rosiglitazone group (-47%, P = 0.02). Myocardial glucose uptake correlated inversely to FFA concentrations both before (r =-0.54, P = 0.002) and after (r = -0.43, P = 0.01) the treatment period in the pooled data. Furthermore, the increase in myocardial glucose uptake correlated inversely with interleukin-6 (IL-6) concentrations (r = -0.58, P = 0.03). CONCLUSIONS: In addition to the improvement in whole body insulin sensitivity, rosiglitazone treatment enhances insulin stimulated myocardial glucose uptake in patients with Type 2 diabetes, most probably due to its suppression of the serum FFAs.

Diabetes Mellitus, Type 2↗

PubMed2004

Insulin induced increase in coronary flow reserve is abolished by dexamethasone in young men with uncomplicated type 1 diabetes.

OBJECTIVE: To examine the role of the sympathetic nervous system in regulating insulin's action on coronary perfusion in uncomplicated type 1 diabetes by blocking centrally mediated sympathetic activity with dexamethasone. METHODS: Positron emission tomography and oxygen 15 labelled water were used to quantify myocardial blood flow basally and during adenosine infusion with or without simultaneous euglycaemic physiological hyperinsulinaemia in nine non-smoking men with type 1 diabetes and 12 healthy non-diabetic men. Each patient was studied both with and without previous dexamethasone treatment for two days (2 mg/day). RESULTS: Insulin increased coronary flow reserve in diabetic (from 4.3 (0.7) to 5.1 (0.6), p < 0.05) and non-diabetic (from 4.3 (0.3) to 5.4 (0.4), p < 0.05) patients. In contrast to non-diabetic patients dexamethasone pretreatment abolished the insulin induced increase in coronary flow reserve in diabetic patients (p < 0.05) leading to lower coronary flow reserve in diabetic than in non-diabetic patients (3.9 (0.6) v 7.1 (0.9), p < 0.05). CONCLUSIONS: These results show that insulin's ability to modulate coronary perfusion is sustained in young patients with type 1 diabetes without microvascular complications or autonomic neuropathy. Dexamethasone treatment abolished the insulin induced increase in coronary flow reserve in diabetic patients but not in healthy study participants, suggesting that sympathetic activation plays an important part in regulating insulin's effects on myocardial perfusion in patients with type 1 diabetes.

Adenosine↗

PubMed2003

Perfusion distribution between and within muscles during intermittent static exercise in endurance-trained and untrained men.

We have recently shown that muscle perfusion varies between different quadriceps femoris muscles during submaximal exercise in humans. In animals, endurance training changes perfusion distribution between muscles during exercise. Whether the same is observed in humans is currently unknown. Therefore, we compared perfusion levels between different parts of the quadriceps femoris muscle group during one-legged intermittent static exercise in seven endurance-trained and seven untrained men. Muscle perfusion was measured using positron emission tomography with [ 15O]-H 2 O. In addition, relative dispersion of perfusion (standard deviation within a region/mean within a region x 100 %) within each muscle region was calculated as an index of perfusion heterogeneity within the muscles. Muscle perfusion tended to be lower in endurance-trained men (p = 0.16) and it was also different between the regions (p < 0.001). However, perfusion distributed similarly between the groups (p = 0.51). Relative dispersion of perfusion within the muscles was lower in endurance-trained men (p = 0.01) and it was also different between muscles (p < 0.001). These results suggest that endurance training does not alter perfusion distribution between muscles, but it decreases perfusion heterogeneity within the muscles.

Adult↗

PubMed2002

The effects of insulin and short-term hyperglycaemia on myocardial blood flow in young men with uncomplicated Type I diabetes.

AIMS/HYPOTHESIS: Insulin enhances coronary vasodilation in healthy subjects. We tested whether insulin is able to induce coronary vasodilation in Type I (insulin-dependent) diabetic mellitus patients. Additionally, the effect of short-term hyperglycaemia on myocardial perfusion was studied. METHODS: Myocardial blood flow was quantitated basally and during adenosine infusion (140 microg/kg per min i.v.) with or without simultaneous insulin infusion (1 mU/kg per min for 60 min) in nine non-smoking Type I diabetic males (HbA(1c) 7.4+/-1.0%) without diabetic complications and 10 healthy non-diabetic otherwise matched males using positron emission tomography and (15)O-water. Diabetic patients were studied on two occasions, once during normoglycaemia (plasma glucose ~6 mmol/l) and once during hyperglycaemia (approximately 10 mmol/l) induced by reducing the dose of insulin for two days. RESULTS: Resting myocardial blood flow was similar in the studied groups (NS). Hyperaemic adenosine stimulated flow was 23% lower in diabetic than in non-diabetic subjects (3.09+/-0.72 vs 4.0+/-1.13 ml x g(-1) x min(-1), p<0.05). Insulin increased significantly adenosine stimulated flow by 23% in diabetic and 17% in non-diabetic subjects (NS between the groups). Hyperglycaemia for two days had no effect on flow values when compared to the values during normoglycaemia (NS). CONCLUSION/INTERPRETATION: Insulin has similar vasodilative effects on coronary arteries in diabetic and non-diabetic subjects. Short-term hyperglycaemia does not alter myocardial blood flow or abolish insulin induced vasodilation in these patients. Insulin induced coronary vasodilation might contribute to the known beneficial effect of intensive insulin therapy on myocardial ischaemia in diabetic patients.

Adenosine↗

PubMed2002

Oestrogen receptor gene variation is a determinant of coronary reactivity in healthy young men.

BACKGROUND: Oxidised low-density lipoprotein (ox-LDL) is a determinant of impaired coronary function and oestrogens inhibit its formation probably throughout genetically-variable oestrogen receptor 1 (ESR1) in artery wall. We hypothesized that the ESR1 polymorphism might influence coronary function and reactivity as measured by positron emission tomography (PET), which allows the detection of coronary dysfunction before appearance of angiographic lesions. MATERIALS AND METHODS: Fifty-one healthy young men (aged 35 +/- 4 years), with normal or slightly-elevated serum cholesterol, underwent PET with intravenous adenosine. ESR1 PvuII genotypes P/P, P/p, and p/p in addition to the plasma autoantibody titre against ox-LDL, a marker of in vivo oxidation, were determined. RESULTS: The ESR1 genotype persisted as the only significant predictor of adenosine stimulated coronary flow (P = 0.035) after adjustment for other coronary risk factors. Subjects with P/P genotype had 33.4 and 41.8% lower adenosine-stimulated flow values than subjects with P/p and p/p genotypes (P = 0.030). Furthermore, plasma levels of ox-LDL titre were on average 59 and 77% higher in subjects with P/P genotype than in subjects with P/p or p/p genotypes (P = 0.049). CONCLUSIONS: These tentative findings from our pilot study provide evidence that genetic variation in ESR1 may modify coronary reactivity and LDL oxidation and reflect differences in the early pathogenesis of coronary dysfunction in these healthy young men.

Adult↗

PubMed2002

High oxidized LDL and elevated plasma homocysteine contribute to the early reduction of myocardial flow reserve in healthy adults.

BACKGROUND: Impairment of coronary blood flow reserve has been shown to be an early manifestation of atherosclerosis and coronary artery disease (CAD). We studied more closely the contribution of various risk factors on early deterioration of coronary function. MATERIALS AND METHODS: Fifty-one young, apparently healthy adults, with normal or mildly elevated serum cholesterol levels but without other major risk factors for CAD, such as diabetes or hypertension, underwent positron emission tomography (PET) studies. Coronary flow reserve (CFR) was measured using O15-water. In addition to the classical risk factors, the role of several new risk indicators, such as low-density lipoprotein (LDL) oxidation, infection (Chlamydia pneumoniae antibodies), and inflammation parameters (adhesion molecules, ICAM, VCAM, selectin, and C-reactive protein), homocysteine and body iron stores were investigated. RESULTS: Elevated lipid and lipoprotein levels were not associated with reduced coronary reactivity. However, high autoantibody titers against oxidized LDL (oxLDL) were associated with 21% lower CFR than low oxLDL (P < 0.05). Furthermore, high homocysteine levels predicted low CFR (P < 0.05). The other measured parameters, Chlamydia pneumoniae antibody levels, C-reactive protein and adhesion molecule concentrations did not associate with myocardial blood flow. In a stepwise regression model, oxLDL (P = 0.03), homocysteine (P = 0.04) and triglycerides (P = 0.018) were significant predictors of CFR. CONCLUSIONS: The present study suggests an important role for oxidized LDL and plasma homocysteine on early impairment of coronary reactivity in young adults.

Adenosine↗

PubMed2002

2-[(18)F]fluoro-2-deoxy-D-glucose combined with microdialysis can be used for the comparison of tissue glucose metabolism in obese and lean rats.

AIMS: Direct assessment of tissue metabolism in vivo is important to understand the pathogenesis of obesity. Labelled glucose analogues are potential candidates to be used for this purpose. The aim of this study was to compare the kinetics and metabolism of 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) in obese (fa/fa) and lean (Fa/?) Zucker rat tissues with microdialysis, and the measurement of uptake and phosphorylation with or without insulin bolus injection. METHODS: Obese (n = 10) and lean (n = 11) anaesthetized rats underwent a microdialysis study after FDG-injection either with or without insulin stimulation. Microdialysis probes were inserted in the jugular vein, quadriceps muscle and liver. After 110 min, tissue [(18)F]-uptake and intracellular phosphorylation of FDG were studied in blood, liver, skeletal muscle, subcutaneous adipose tissue, intra-abdominal adipose tissue and hypothalamus. RESULTS: When measured with microdialysis, insulin-enhanced FDG disappeared from the blood pool and interstitial space of skeletal muscle and liver more effectively in lean rather than in obese animals. Insulin-stimulated skeletal muscle and adipose tissue[(18)F]-uptake was impaired in obese Zucker rats compared with lean animals. Hypothalamic FDG uptake was six to sevenfold higher than in other measured tissues, but was attenuated in obese rats. In liver and in mesenteric fat, insulin-enhanced FDG phosphorylation in lean rats compared with obese animals. CONCLUSIONS: Positron-emitting glucose analogue FDG, combined with microdialysis and tissue analysis, is a feasible method in studying glucose metabolism at the cellular level in animal studies.

Animals↗