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Biomedical subjects

E Moberg

Publications and source records attributed to E Moberg.

At least 19 recordsLinked to original sources
PubMed2001

Evidence for a major role of skeletal muscle lipolysis in the regulation of lipid oxidation during caloric restriction in vivo.

A lipolytic process in skeletal muscle has recently been demonstrated. However, the physiological importance of this process is unknown. We investigated the role of skeletal muscle lipolysis for lipid utilization during caloric restriction in eight obese women before and after 11 days of very low-calorie diet (VLCD) (2.2 MJ per day). Subjects were studied with indirect calorimetry and microdialysis of skeletal muscle and adipose tissue in order to analyze substrate utilization and glycerol (lipolysis index) in connection with a two-step euglycemic-hyperinsulinemic (12 and 80 mU/m(2). min) clamp. Local blood flow rates in the two tissues were determined with (133)Xe-clearance. Circulating free fatty acids and glycerol decreased to a similar extent during insulin infusion before and during VLCD, and there was a less marked insulin-induced reduction in lipid oxidation during VLCD. Adipose tissue glycerol release was hampered by insulin infusion to the same extent ( approximately 40%) before and during VLCD. Skeletal muscle glycerol release was not influenced by insulin before VLCD. However, during VLCD insulin caused a marked (fivefold) (P < 0.01) increase in skeletal muscle glycerol release. The effect was accompanied by a fourfold stimulation of skeletal muscle blood flow (P < 0.01). We propose that, during short-term caloric restriction, the reduced ability of insulin to inhibit lipids, despite a preserved antilipolytic effect of the hormone in adipose tissue, is caused by an augmented mobilization of fat from skeletal muscle, and that a physiological role of muscle lipolysis provides a local source of fatty acids.

Adipose Tissue↗
PubMed2000

Rates of skeletal muscle and adipose tissue glycerol release in nonobese and obese subjects.

Skeletal muscle and adipose tissue lipolysis rates were quantitatively compared in 12 healthy nonobese and 14 insulin-resistant obese subjects for 3.5 h after an oral glucose load using microdialysis measurements of interstitial glycerol concentrations and determinations of local blood flow with 133Xe clearance in the gastrocnemius muscle and in abdominal subcutaneous adipose tissue. Together with measurements of arterialized venous plasma glycerol, the absolute rates of glycerol mobilization were estimated. In the basal state, skeletal muscle and adipose tissue glycerol levels were 50% higher (P < 0.05-0.01) and adipose tissue blood flow (ATBF) and muscle blood flow (MBF) rates were 30-40% lower (P < 0.02-0.05) in obese versus nonobese subjects. After glucose ingestion, adipose tissue glycerol levels were rapidly and transiently reduced, whereas in muscle, a progressive and less pronounced fall in glycerol levels was evident. MBF remained unchanged in both study groups, whereas ATBF increased more markedly (P < 0.01) in the nonobese versus obese subjects after the oral glucose load. The fasting rates of glycerol release per unit of tissue weight from skeletal muscle were between 20 and 25% of that from adipose tissue in both groups. After glucose ingestion, the rates of glycerol release from skeletal muscle and from adipose tissue were almost identical in nonobese and obese subjects. However, the kinetic patterns differed markedly between tissues; in adipose tissue, the rate of glycerol mobilization was suppressed by 25-30% (P < 0.05) after glucose ingestion, whereas no significant reduction was registered in skeletal muscle. We conclude that significant amounts of glycerol are released from skeletal muscle, which suggests that muscle lipolysis provides an important endogenous energy source in humans. In response to glucose ingestion, the regulation of skeletal muscle glycerol release differs from that in adipose tissue; although the rate of glycerol release from adipose tissue is clearly suppressed, the rate of glycerol mobilization from skeletal muscle remains unaltered. In quantitative terms, the rate of glycerol release per unit of tissue weight in adipose tissue and in skeletal muscle is similar in nonobese and obese subjects in both the postabsorptive state and after glucose ingestion.

Adipose Tissue↗
PubMed1998

Lipolytic response during spontaneous hypoglycaemia in insulin-dependent diabetic subjects.

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.

Adipose Tissue↗
PubMed1998

Importance of phosphodiesterase 3 for the lipolytic response in adipose tissue during insulin-induced hypoglycemia in normal man.

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.

Adipose Tissue↗
PubMed1998

beta-Adrenergic regulation of lipolysis and blood flow in human skeletal muscle in vivo.

Little is known about the regulation of catecholamine-stimulated lipolysis in human skeletal muscle. Therefore, beta-adrenergic regulation of lipolysis and blood flow was investigated in healthy subjects in vivo by use of microdialysis of the gastrocnemius muscle. First, during a hypoglycemic, hyperinsulinemic clamp, which induces a lipolytic response in skeletal muscle tissue, the muscle was locally perfused with beta-adrenoceptor blocking agents. Perfusion with nonselective (propranolol) and beta2-selective (ICI-118551) blocking agents counteracted the hypoglycemia-induced lipolysis (P < 0.01), but perfusion with metoprolol (beta1-blocker) did not affect the glycerol response. Second, selective beta-adrenoceptor agonists were perfused in situ into skeletal muscle during resting conditions. beta2-Adrenoceptor stimulation with terbutaline induced a concentration-dependent increase in skeletal muscle glycerol levels and in tissue blood flow, whereas perfusion with beta1- or beta3-adrenoceptor agonists (dobutamine or CGP-12177) did not influence the glycerol concentration or blood flow. In conclusion, in skeletal muscle tissue, only the beta2-subtype is of importance among beta-adrenoceptors for regulation of lipolysis and blood flow. This is in contrast to adipose tissue, where beta1- and beta3-adrenoceptors are also involved.

Adrenergic beta-Antagonists↗
PubMed1997

Protracted glucose fall in subcutaneous adipose tissue and skeletal muscle compared with blood during insulin-induced hypoglycaemia.

The absolute glucose concentrations in subcutaneous adipose tissue and skeletal muscle were determined with microdialysis in 10 normal-weight, healthy subjects during a standardized hyperinsulinaemic hypoglycaemic clamp. The concentration of tissue dialysate glucose was measured in 15-min fractions and compared with that in arterialized venous plasma. Insulin (0.15 U x kg(-1) x h[-1]) was infused i.v. to lower the plasma glucose level to 2.5 mmol/l over 30 min. This level was maintained for 30 min by using a variable glucose infusion. Thereafter, the insulin infusion was stopped and the plasma glucose level was gradually increased to baseline levels over 120 min. During a 60-min basal period, the glucose levels in muscle were 0.6 mmol/l lower than those in plasma (p = 0.002), whereas the levels in adipose tissue and plasma were similar. The glucose nadirs in muscle (1.6 +/- 0.1 mmol/l) and adipose tissue (2.0 +/- 0.1 mmol/l) were significantly lower than that in plasma (2.4 +/- 0.1 mmol/l) (p = 0.001 and 0.02, respectively), and the time-to-nadir was substantially longer in muscle (69 +/- 5 min) and adipose tissue (57 +/- 2 min) than in plasma (39 +/- 3 min) (p = 0.0004). When the insulin infusion was stopped, the increases in adipose tissue and muscle glucose concentrations were delayed by approximately 25 and 45 min, respectively, as compared to the increase in plasma glucose. Thus, it seems that glucose measurements in adipose tissue and muscle more adequately reflect overall tissue homeostasis than do measurements in blood and that clinically relevant tissue glucopenia may be overlooked by conventional blood glucose measurements.

Adipose Tissue↗
PubMed1997

Detection of hypoglycaemia by microdialysis measurements of glucose in subcutaneous adipose tissue.

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.

Adipose Tissue↗
PubMed1997

Absolute concentrations of glycerol and lactate in human skeletal muscle, adipose tissue, and blood.

The absolute concentrations of glycerol and lactate were studied with microdialysis of adipose tissue and skeletal muscle in normal-weight subjects. The basal interstitial glycerol concentration was 232 +/- 33, 96 +/- 8, and 59 +/- 6 mumol/l in fat, muscle, and arterialized plasma, respectively (P = 0.0002). This relationship was maintained during both euglycemic hyperinsulinemia, when glycerol decreased in all three compartments, and hypoglycemia, when glycerol first decreased and then increased in fat, muscle, and blood (P = 0.0001 for both). Basal interstitial lactate concentrations were similar in adipose tissue (1.1 +/- 0.2 mmol/l) and skeletal muscle (1.9 +/- 0.4 mmol/l) and higher than in arterialized blood (0.6 +/- 0.1 mmol/l, P = 0.002). During hyperinsulinemia and hypoglycemia, lactate increased (P = 0.0001) and the tissue-blood relationship was maintained (P = 0.04). In conclusion, adipose tissue and skeletal muscle mobilize glycerol and lactate at rest. Glycerol and lactate production are influenced by hyperinsulinemia and hypoglycemia in both tissues. Adipose tissue appears to be the major site of glycerol production, whereas skeletal muscle and fat may be equally important for lactate production.

Adipose Tissue↗
PubMed1996

Acute effects of the alpha 2-adrenoreceptor antagonist idazoxan on hormonal responses and symptoms of hypoglycaemia in patients with type 1 diabetes mellitus.

The aim of the present study was to evaluate the effect of the alpha 2-adrenoceptor antagonist idazoxan on hormonal responses and hypoglycaemia symptoms in patients with insulin-dependent (Type 1) diabetes mellitus. Six male Type 1 diabetic patients were studied with and without intravenous infusion of idazoxan. Hypoglycaemia was induced by an intravenous infusion of insulin (100 mU.kg-1.h-1), together with a glucose clamp, to obtain an arterialised venous blood glucose level of 2.3 mmol/l. Idazoxan was given at a dose of 295 micrograms/kg. Venous blood samples were obtained for analyses of free insulin, growth hormone (GH), glucagon and catecholamines. Symptoms were scored on a visual-analogue rating scale. Areas under the curves with and without idazoxan were respectively 22.4 +/- 7.0 vs 33.0 +/- 9.6 micrograms.l-1.h (p = 0.17) for GH, 4.1 +/- 1.1 vs 2.4 +/- 0.9 nmol.l-1h (p < 0.05) for adrenaline, 5.6 +/- 0.9 vs 1.3 +/- 0.5 nmol.l-1.h (p < 0.05) for noradrenaline and 51 +/- 38 vs -40 +/- 11 ng.l-1.h (p < 0.05) for glucagon. Sweating and palpitations were more pronounced during idazoxan infusion than during the control test. It is concluded that idazoxan increases catecholamine and glucagon responses as well as some of the warning signals of hypoglycaemia in Type 1 diabetic patients, whereas the GH response seems less affected by idazoxan.

Adrenergic alpha-Antagonists↗
PubMed1995

Day-to-day variation of insulin sensitivity in patients with type 1 diabetes: role of gender and menstrual cycle.

The aim of the present study was to compare the day-to-day variations of the insulin sensitivity in male and female Type 1 diabetic patients and to assess the insulin sensitivity in the follicular and luteal phases of the menstrual cycle. Ten male and 20 female Type 1 diabetic patients participated in the study. The insulin sensitivity was assessed by the insulin (0.4 mU kg-1 min-1)-glucose/(4.5 mg kg-1 min-1)-infusion test (IGIT). In 5 of the female patients, a simultaneous i.v. influsion of somatostatin (100 micrograms h-1) was given (SIGIT). Each patient was studied twice, with 2 weeks separating the two tests. The day-to-day variations of the insulin sensitivity were almost identical in the male and female patients, the coefficients of variation being 13% in both groups. In 15 of the female patients, ovulation occurred. In these women, the mean blood-glucose levels between 120 and 240 min after the onset of the IGIT/SIGIT were 9.8 +/- 1.1 mmol l-1 in the follicular phase and 10.3 +/- 1.0 mmol l-1 in the luteal phase, n.s. (95% confidence interval for the difference (luteal-follicular) -0.8-1.9 mmol l-1). Although the present study cannot exclude minor changes of insulin sensitivity during the menstrual cycle, our results suggest that the changes of the metabolic control during the menstrual cycle, experienced by many women with Type 1 diabetes, are largely attributable to mechanisms other than variations of insulin sensitivity.

Adult↗
PubMed1994

Acute mental stress impairs insulin sensitivity in IDDM patients.

The effect of acute mental stress on insulin sensitivity was evaluated in ten IDDM patients, studied on two occasions (test day and control day) in random order and separated by a period of 1-3 weeks. Mental stress was evoked by a modified filmed version of Stroop's CWT for 20 min. On the control day, the patients were resting quietly during the corresponding period. Insulin sensitivity was estimated by an insulin (0.4 mU.kg-1 x min-1)-glucose (4.5 mg.kg-1 x min-1)-infusion test (IGIT) for 6.5 h. Mental stress evoked significant responses for adrenaline, cortisol and GH, their respective peak values being 0.27 +/- 0.05 nmol/l, 426 +/- 27 nmol/l and 7.6 +/- 1.8 micrograms/l, as well as increases in systolic and diastolic blood pressure and pulse rate The steady-state blood glucose levels, i.e. the mean blood glucose levels 3-6.5 h after the start of the IGIT, were significantly higher after stress, compared with those on the control day, 10.6 +/- 1.5 vs 8.7 +/- 1.4 mmol/l, p = 0.01, demonstrating impairment of the insulin sensitivity by mental stress. It is concluded that acute mental stress induces a state of insulin resistance in IDDM patients, which can be demonstrated by an IGIT to appear 1 h after maximal stress and to last more than 5 h.

Acute Disease↗
PubMed1993

How accurate are home blood-glucose meters with special respect to the low glycemic range?

Comparisons were made between four blood-glucose meters (Diascan, Glucometer II, Reflolux II and ExacTech) and a reference method (YSI) for the full, clinical, blood-glucose range and for the subranges < 4.4 mmol/l, 4.4-10.0 mmol/l and > 10.0 mmol/l, respectively. In the low-glucose range, the error-grid analysis was also applied. All the meters showed acceptable agreement with the reference method when the whole glucose range was considered, yielding r-values between 0.96 and 0.99. However, when the results were separated in the different subranges, the outcome was different, in that the Diascan meter displayed systematically high glucose levels and the ExacTech meter showed a great spread of the values within the low-glucose range, whereas the Glucometer II and the Reflolux II meter were less accurate within the high-glucose range. By applying the error-grid analysis, several errors of clinical importance within the low glycemic range were revealed, while other significant errors, which might lead to inadequate therapeutic decisions, were classified as 'clinically accurate'.

Blood Glucose↗
PubMed1993

Estimation of blood-glucose variability in patients with insulin-dependent diabetes mellitus.

The aim of the study described here was to evaluate the standard deviation (SD) as a measure of blood-glucose variability in IDDM patients under 'normal life' conditions. One hundred IDDM patients performed self-monitoring of blood glucose (SMBG) five times every 2 days for 4 weeks. From these records the following measurements were calculated for each patient: the standard deviation of all blood-glucose values (SDBG), the M-value, the percentage of values < 3 and > 15 mmol l-1 (PE), and the mean, absolute difference of consecutive blood-glucose values (MAD), a novel measure of blood-glucose variability, also taking into consideration the succession of the values. Before the study the patients as well as their physicians were asked to estimate the blood-glucose stability of the patient, using a five-category scale of statements. The patients recorded an average of 64 (range: 32-70) SMBG values. The SDBG was normally distributed with a mean of 3.9 +/- 1.0 mmol l-1. There was a highly significant correlation between the SDBG and the other measures of blood-glucose variability (p = 0.0001, r > 0.8). It appeared that the variation of the SMBG values recorded before dinner contributed to the total glucose variability to a great extent. There was a poor agreement between the subjective estimations of the blood-glucose stability made by the patients and the physicians and the objective measures of the blood-glucose variability. It is concluded that the SD provides an accurate and easily available estimate of blood-glucose variability in IDDM patients practising home blood-glucose monitoring.

Adult↗
PubMed1992

Arterial, arterialized venous, venous and capillary blood glucose measurements in normal man during hyperinsulinaemic euglycaemia and hypoglycaemia.

The purpose of this study was to evaluate the effectiveness of the warm-air box method on the arterialization of venous blood during euglycaemia and hypoglycaemia. Six healthy male volunteers were studied using an i.v. infusion of insulin (144 mU.kg-1.h-1). Arterial blood glucose was clamped at the baseline level for the first 30 min and subsequently reduced to 3.2 and to 2.5 mmol/lf or 20 min. At each stage, including prior to insulin infusion, arterial, arterialized venous (heating the hand in a warm-air box set to 55-60 degrees C), venous and capillary blood samples were taken simultaneously for analyses of blood glucose and oxygen saturation (not for capillary blood). The oxygen saturations in arterialized blood were approximately 3% below the arterial values. The arterial-arterialized difference of blood glucose was about 0.1 mmol/l (the 95% confidence interval: from -0.19 to 0.41 mmol/l), which tended to correlate with the difference in oxygen saturations between the arterial and arterialized blood samples (r = 0.25, p = 0.08). During the test the forearm venous blood oxygen saturation increased by 9% and the arteriovenous difference in blood glucose ranged from 0.2 to 0.5 mmol/l which correlated significantly with the difference in oxygen saturations (r = 0.48, p less than 0.001). Capillary glucose was similar to the arterialized value. Rectal temperature was stable during the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The hyperflexed seemingly useless tetraplegic hand: a method of surgical amelioration.

In a series of 65 tetraplegic hands with severe disabling spasticity and/or flexion contracture, selective flexor tendon elongation procedures were employed to improve their static and kinetic postures. A kinetic approach was adopted, utilizing local anesthesia in a wide-awake patient. This was employed to allow for the patient's cooperation in determining at surgery the desired length of digital extension at the time of wrist tenodesis action. Elongation of the extensor digitorum communis (EDC), extensor indicis proprius (EIP), and extensor digiti quinti (ED V) were added to correct an 'extrinsic-plus' posture observed in 16 patients following flexor tendon lengthening. With the resultant improvement in the static posture of the digits, tendon transfers could then be employed to provide a more functional tenodesis action. These measures provided both improved palmar contact and prehension.

Adolescent↗
PubMed1991

Insulin absorption is faster when keeping the infusion site in use for three days during continuous subcutaneous insulin infusion.

To evaluate the possible influence of regular infusion site changes on insulin absorption, fifteen type 1 diabetic patients using continuous subcutaneous insulin infusion (CSII) were studied on four occasions: the first day after an infusion site was settled, again the first day after a new infusion site was utilized and the two fourth days after the two infusion sites had been used for three days. A bolus of insulin (1 U/10 kg of body weight) was infused by the pump in the lower para-umbilical region. Plasma free insulin and blood glucose levels were determined before and during 240 min of the study at 30-min intervals. It was found that the peak times extracted from the individual insulin curves were shorter in 17 out of 23 curves when the fourth day was compared with the first day and the mean value of peak time of the fourth day was significantly shorter than that of the first day (56 +/- 11 vs 110 +/- 15 min, P less than 0.01). The mean area under the insulin curves during the first hour of the study tended to increase on the fourth day compared to that of the first day (25 +/- 2.2 vs 21 +/- 2.1 mU.l-1.min, P = 0.12). The decremental area of blood glucose on the fourth day was larger than on the first day (405 +/- 111 vs 82 +/- 160 mmol.l-1.min, P less than 0.05). We conclude that during CSII, the absorption rate of the injected insulin bolus is faster when the infusion site has been in use continuously for three days.

Absorption↗
PubMed1991

Insulin clearance during hypoglycemia in patients with insulin-dependent diabetes mellitus.

Eight male patients with insulin-dependent diabetes mellitus (IDDM) without residual beta-cell function were studied on two occasions in random order. In one experiment hypoglycemia was induced by a constant rate iv infusion of insulin (0.034 U/kg/h) during 150 minutes. At the other occasion an identical infusion of insulin was given, but this time euglycemia was maintained by a variable iv infusion of glucose. Plasma levels of free insulin were almost identical during the two experiments indicating that insulin clearance is not influenced by hypoglycemia in patients with IDDM.

Adult↗