يعرض 1 - 10 نتائج من 10 نتيجة بحث عن '"E Hagström-Toft"', وقت الاستعلام: 2.05s تنقيح النتائج
  1. 1

    المصدر: The Journal of Clinical Endocrinology & Metabolism. 93:240-246

    الوصف: Context: The regulation of lactate production in skeletal muscle (SM) and adipose tissue (AT) is not fully elucidated. Objective: Our objective was to investigate the catecholamine-mediated regulation of lactate production and blood flow in SM and AT in healthy, normal-weight subjects by using microdialysis. Methods: First, lactate levels in SM and AT were measured during an iv norepinephrine infusion (n = 11). Local blood flow was determined with the 133Xe-clearance technique. Second, muscle lactate was measured during hypoglycemia and endogenous epinephrine stimulation (n = 12). Third, SM was perfused with selective β1–3-adrenoreceptor agonists in situ (n = 8). Local blood flow was measured with the ethanol perfusion technique. Results: In response to iv norepinephrine, the fractional release of lactate (difference between tissue and arterial lactate) increased by 40% in SM (P = 0.001), whereas remaining unchanged in AT. Blood flow decreased by 40% in SM (P < 0.005) and increased by 50% in AT (P < 0.05). In response to hypoglycemia, epinephrine increased 10-fold, and the fractional release of lactate in SM doubled (P < 0.0001). The blood flow remained unchanged. The β2-agonist, terbutaline, caused a marked concentration-dependent increase of muscle lactate and blood flow (P < 0.0001). The β1-agonist, dobutamine, induced a discrete increase of muscle lactate (P < 0.0001), and the blood flow remained unchanged. The β3-agonist, CPG 12177, did not affect muscle lactate or blood flow. Conclusions: Catecholamines stimulate lactate production in SM, but not in AT. In SM, the β2-adrenoreceptor is the most important β-adrenergic receptor subtype in the regulation of lactate production.

  2. 2

    المصدر: The Journal of Clinical Endocrinology & Metabolism. 89:4693-4700

    الوصف: Effects of circulating insulin and glucose concentrations on skeletal muscle and adipose tissue lipolytic activity were investigated in 10 type 1 diabetes patients with no endogenous insulin secretion. Microdialysis measurements of interstitial glycerol and determination of fractional glycerol release were carried out during standardized combinations of relative hypoinsulinemia/moderate hyperglycemia (11 mmol/liter), hyperinsulinemia/ normoglycemia (5 mmol/liter), and hyperinsulinemia/moderate hyperglycemia, respectively. Local tissue blood flow rates were measured with the (133)Xe clearance technique. In response to the change from hypo- to hyperinsulinemia, the fractional release of glycerol decreased from 159.6 +/- 17.8 to 85.1 +/- 13.7 micromol/liter (P < 0.0001) in adipose tissue, whereas it remained unchanged in skeletal muscle (44.6 +/- 6.4 vs. 36.0 +/- 7.4 micromol/liter; not significant). When hyperinsulinemia was combined with hyperglycemia, fractional glycerol release was further reduced in adipose tissue (64.5 +/- 12.2 micromol/liter; P < 0.05), and in this situation it was also markedly decreased in skeletal muscle (18.1 +/- 4.8 micromol/liter; P < 0.0001). Skeletal muscle blood flow was unaltered over the respective study periods. Adipose tissue blood flow decreased by 50% in response to hyperinsulinemia (P < 0.0005), but no further change was seen when hyperinsulinemia was combined with hyperglycemia. It is concluded that in patients with type 1 diabetes, insulin does not exert an antilipolytic effect in skeletal muscle during normoglycemia. However, in response to combined hyperinsulinemia and hyperglycemia, the lipolytic activity in skeletal muscle is restrained in a similar way as in adipose tissue. This may be explained by a glucose-mediated potentiation of the antilipolytic effectiveness of insulin.

  3. 3

    المصدر: The Journal of Clinical Endocrinology & Metabolism. 86:1229-1234

    الوصف: In vitro and animal studies have shown that glucagon and glucagon-like peptide-1 (GLP-1)-(7-36) amide may participate in the regulation of lipolysis. However, results on human subjects in vivo are inconclusive. To avoid confounding effects, such as changes in insulin secretion when perfusing hormones iv, we used the in situ microdialysis to analyze the impact of human glucagon and GLP-1 on lipolysis rates and local blood flow. Nine healthy volunteers were given an 80-min local perfusion of each hormone (10(-6) mol/L), both in skeletal muscle (gastrocnemius) and in sc abdominal adipose tissue, after a basal period with perfusion of Ringer's solution. Variations in the lipolysis rate and blood flow, respectively, were assessed by measuring of the dialysate glycerol content and the ethanol ratio (outgoing-to-ingoing ethanol concentration). The in vitro relative recovery of the microdialysis probes was 5.2 +/- 1.2%. No significant effects of either GLP-1 or glucagon on either lipolysis rate or blood flow were detected in muscle or adipose tissue. Isoprenaline (10(-6) mol/L), which was perfused after glucagon or GLP-1 in the same catheters, significantly increased the lipolysis rate (a 249% increase of dialysate glycerol in adipose tissue and a 72% increase in skeletal muscle). Furthermore, isoprenaline, but not glucagon or GLP-1, stimulated lipolysis in vitro in isolated human sc adipose tissue. We conclude that neither glucagon nor GLP-1 affect the lipolysis rate of human sc adipose tissue or skeletal muscle.

  4. 4

    المصدر: Hormone and Metabolic Research. 30:684-688

    الوصف: The present investigation aimed to clarify the role of phosphodiesterase (PDE) type 3 for in vivo lipolysis in human adipose tissue during simultaneous insulin and catecholamine stimulation. Therefore, ten healthy subjects were investigated during insulin-induced hypoglycemia. Microdialysis probes were implanted in the subcutaneous adipose tissue and perfused by solvents with or without addition of the specific PDE 3 antagonist amrinone. Furthermore, changes in the local blood flow surrounding the dialysis probes were assessed by the ethanol escape technique. During the 60 min period before the start of the insulin infusion, adipose tissue glycerol levels (lipolysis index) increased significantly when amrinone was added to the perfusate (p = 0.0006, one-factor ANOVA). The antilipolytic response to the early phase of insulin infusion decreased (delta glycerol 9.0+/-3.5 vs. 29.9+/-6.0 micromol/l, p = 0.04) and the lipolytic response after hypoglycemia increased (AUC 122.4+/-18.0 vs. 13.4+/-16.3 micromol x l(-1) x h, p = 0.0001) comparing the experiments with or without amrinone, respectively. When amrinone was excluded from the perfusate, there was an increase in the nutritive blood flow during hypoglycemia, whereas there were no significant changes in the local blood flow surrounding the probe when amrinone was added to the perfusate. In conclusion, during insulin-induced hypoglycemia, PDE 3 activation clearly counteracts the lipolytic effect of catecholamines. When PDE 3 is specifically blocked, lipolysis increases greatly. Thus, PDE 3 is important for the in vivo regulation of the antilipolytic and lipolytic responses to hormones in human adipose tissue.

  5. 5

    المصدر: Hormone and Metabolic Research. 29:440-443

    الوصف: The aim of the present investigation was to study how various fractional sampling times affect the detection of hypoglycaemia, using microdialysis of the adipose tissue. We therefore studied eight healthy subjects during a standardized hyperinsulinaemic hypoglycaemic clamp. The glucose concentration in the adipose tissue dialysate was determined in timed fractions of 15 min, 30 min and 60 min and compared to those in arterialized venous plasma. Before and after hypoglycaemia, the plasma and adipose tissue glucose concentrations were similar. However, during hypoglycaemia, the adipose tissue glucose nadir, as measured in 15-min fractions of the tissue dialysate, was significantly lower than that in plasma (2.1 +/- 0.1 vs. 2.4 +/- 0.1 mmol/l, p = 0.05) and during the increase in plasma glucose, the corresponding increase in adipose tissue glucose was delayed by approximately 20 min (p = 0.004). When the microdialysate was sampled over 30 or 60 min periods, there was a close agreement between the plasma and adipose tissue glucose nadirs. We conclude that there is a protracted fall in subcutaneous adipose tissue glucose levels in response to insulin-induced hypoglycaemia. While shorter microdialysis sampling periods improve the resolution of the hypoglycaemic event, 30-min fractions seem sufficient to detect hypoglycaemia in a clinically relevant way.

  6. 6

    المصدر: The Journal of clinical endocrinology and metabolism. 96(4)

    الوصف: Context:The mechanisms behind the positive effects of physical activity on glucose metabolism in skeletal muscle and the time course of the effects need to be more elucidated.Objective:The aim was to examine the prolonged effects of an acute bout of one-legged exercise on local skeletal muscle glucose utilization and tissue perfusion.Design and Setting:Interstitial glucose concentration, local tissue perfusion, glucose uptake, and effects of insulin infusion were studied 12 h after an acute bout of exercise and without prior exercise.Participants:Ten healthy subjects, five women and five men, participated in the study.Intervention:Microdialysis measurements, 133Xe clearance, and a 2-h hyperinsulinemic euglycemic clamp were performed on two occasions.Main Outcome Measures:We measured interstitial glucose concentration and tissue perfusion in the quadriceps femoris muscle of both legs.Results:Tissue perfusion (3.3 ± 0.6 ml × 100 g−1 × min−1vs. 1.4 ± 0.2 ml × 100 g−1 × min−1; P = 0.007) and basal glucose uptake (2.3 ± 0.5 μmol × 100 g−1 × min−1vs. 0.9 ± 0.2 μmol × 100 g−1 × min−1; P = 0.006) were increased in the leg that had exercised compared to the resting leg; the findings in the resting leg were comparable to those in the control experiment without prior exercise. The relative effect of insulin on fractional skeletal muscle glucose uptake was the same in all experimental settings, and insulin did not affect tissue perfusion.Conclusions:The prolonged stimulatory effect of physical exercise on skeletal muscle glucose uptake was mediated via vascular effects combined with an increase in basal glucose transport independent of enhancement of insulin responses.

  7. 7

    المصدر: European Journal of Clinical Investigation. 23:837-844

    الوصف: The influence of insulin on lipolysis and glucose metabolism in abdominal adipose tissue was studied in situ with the microdialysis technique during a euglycaemic insulin clamp (1 mU kg-1 min-1) in nine cirrhotic patients and 10 controls. The cirrhotic patients displayed a 50% decrease in glucose utilization rate during the clamp (P < 0.001). Dialysate glucose levels decreased similarly by 20-30%., in patients and controls, which in the presence of unchanged local blood flow in the adipose tissue in response to insulin, is at hand with a glucose uptake into the adipocytes of similar magnitude in both groups. Before and during the clamp, the arterial and dialysate levels of glycerol were higher in the patients than in the control subjects (ANOVA P = 0.001 and 0.048 in arterial blood and dialysate, respectively). In relative terms, however, insulin induced a 70% reduction of arterial and dialysate glycerol in both groups. The concentrations of lactate and pyruvate in the dialysate and blood increased in a similar way in both groups during hyperinsulinaemia. The results suggest an increased rate of lipolysis in cirrhotic patients. Insulin cannot lower it to normal, although it is still capable of achieving a relative reduction. No explanation was found in the adipose tissue to the insulin resistance to whole-body glucose utilization that was noted in the patients with cirrhosis.

  8. 8

    المصدر: The Journal of clinical endocrinology and metabolism. 91(2)

    الوصف: Triglyceride (TG) deposits in skeletal muscle (SM) are an important energy reservoir, and increased im TG content is associated with muscle insulin resistance.The objective of the study was to investigate the effect of endogenous catecholamines on TG lipolysis in human SM in vivo. Adipose tissue (AT) was studied for comparison.Glycerol levels (index of lipolysis) were measured using microdialysis in the gastrocnemius muscle and abdominal sc adipose tissue during a hyperinsulinemic, hypoglycemic clamp (n = 13) and in response to in situ perfusion of epinephrine and norepinephrine (10(-10) to 10(-5) m) (n = 12). Local tissue blood flow was monitored with the ethanol perfusion technique.This was an experimental study.The study population consisted of healthy subjects.Plasma epinephrine increased 10-fold and plasma norepinephrine 2-fold in response to insulin-induced hypoglycemia. In parallel, the fractional glycerol release (difference between tissue and arterial glycerol) increased 2-fold in both tissues (P0.0001). No changes in AT and SM blood flow were registered. When the catecholamines were perfused in situ, tissue glycerol increased significantly at 10(-7) m of either epinephrine and norepinephrine (P0.0001) in AT. The maximum stimulation was seen at 10(-6) m norepinephrine (2-fold increase) and 10(-5) m epinephrine (3-fold increase). In SM, tissue glycerol increased at 10(-7) m epinephrine and 10(-6) m norepinephrine, respectively (P0.0001); the maximum increase of glycerol values (at 10(-6) m) was 2.5 times for epinephrine and 1.6 times for norepinephrine, respectively (P0.01).The lipolytic activity of SM is increased by endogenous catecholamines in vivo and appears to be more responsive to epinephrine than norepinephrine stimulation.

  9. 9

    المصدر: The Journal of clinical endocrinology and metabolism. 90(2)

    الوصف: Release of glycerol and free fatty acids (FFA) was investigated in human skeletal muscle strips. In the basal state, glycerol and FFA were released at almost equimolar rates (0.3 nmol/ng tissue.90 min). A nonselective beta-adrenoceptor agonist, isoprenaline, caused a concentration-dependent stimulation of glycerol release, whereas FFA release was unaffected. Basal and isoprenaline-induced glycerol release correlated positively with the age of the donors (r = 0.5, P0.005) but not with their body mass index (Por = 0.4). Biochemical experiments with hormone-sensitive lipase (HSL) showed that most enzyme activity was both in the cytosol and mitochondrial fraction and that it constituted the common long and active form of the protein. Electron microscopy studies in rat skeletal muscle using labeled highly specific HSL antibodies verified the cytosolic location of HSL and, furthermore, indicated an accumulation of HSL-adjoining mitochondria. These results suggest that FFA produced in myocytes during catecholamine-induced lipolysis are retained by the muscle and, therefore by inference, reused. It is conceivable that efficient hydrolysis of acylglycerol by HSL located in the cytosol as well as near the mitochondria may facilitate mitochondrial FFA oxidation. In addition, muscle lipolysis activity increases during aging and may be independent of total body fat.

  10. 10

    المؤلفون: Hellström L, E Hagström-Toft, Moberg E

    المصدر: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 30(9)

    الوصف: The adipose tissue lipolytic response to spontaneous, non-experimental hypoglycaemic episodes was investigated in patients with IDDM during ordinary life conditions. The absolute concentration of glucose and glycerol in subcutaneous adipose tissue was monitored in mobile patients with microdialysis in 16 IDDM subjects. The absolute glycerol level in adipose tissue was about five times as high as in venous plasma, whereas the glucose concentration was almost the same in the two compartments. Fourteen hypoglycaemic episodes (glucose < 3.5 mmol/l) were recorded. Adipose tissue glycerol increased markedly by 75 % in response to hypoglycaemia and remained increased during at least 4 hours following glucose nadir (F = 3.70, p = 0.003). The circulating levels of free fatty acids increased about three-fold in parallel to the in situ lipolytic response (F = 2.98, p = 0.025). The same lipolytic response was observed whether or not the hypoglycaemic event was perceived by the patient. A rapid decrease in glucose concentration above hypoglycaemic levels did not affect the adipose tissue dialysate glycerol. It is concluded that spontaneous hypoglycaemia elicits a long-term lipolytic response in adipose tissue as evidenced by increased levels of glycerol in adipose tissue with a parallel increase in serum free fatty acids. However, lipolysis is not activated by a rapid glucose decrease per se. The microdialysis method can be used to characterise the lipolytic response to hypoglycaemic episodes in every day life of IDDM patients.