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Biomedical subjects

L Simonsen

Publications and source records attributed to L Simonsen.

At least 19 recordsLinked to original sources

Exendin-4, but not glucagon-like peptide-1, is cleared exclusively by glomerular filtration in anaesthetised pigs.

AIMS/HYPOTHESIS: The insulinotropic hormone, glucagon-like peptide-1 (GLP-1), is rapidly degraded in vivo as a result of the combination of extensive enzymatic degradation and renal extraction. The GLP-1 receptor agonist, exendin-4, has a longer duration of action, and has recently been approved as a new agent for the treatment of type 2 diabetes mellitus. Exendin-4 is less prone to enzymatic degradation, but it is still unclear what other factors contribute to the increased metabolic stability. MATERIALS AND METHODS: The overall metabolism of GLP-1 and exendin-4 was directly compared in anaesthetised pigs (n=9). RESULTS: Metabolism of GLP-1 (C-terminal RIA; t (1/2) 2.0+/-0.2 min, metabolic clearance rate [MCR] 23.2+/-2.8 ml min(-1) kg(-1); N-terminal RIA; t (1/2) 1.5+/-0.2 min, MCR 88.1+/-10.6 ml min(-1) kg(-1)) was significantly faster than the metabolism of exendin-4 (t (1/2) 22.0+/-2.1 min, p<0.0001; MCR 1.7+/-0.3 ml min(-1) kg(-1), p<0.01). Differences in arteriovenous concentrations revealed organ extraction of GLP-1 by the kidneys (C-terminal 56.6+/-2.6%; N-terminal 48.3+/-5.9%), liver (N-terminal 41.4+/-3.8%), and peripheral tissues (C-terminal 42.3+/-6.0%; N-terminal 33.0+/-7.8%), whereas organ extraction of exendin-4 was limited to the kidneys (21.3+/-4.9%). While the renal extraction of exendin-4 (6.9+/-2.5 pmol/min) did not differ significantly from the amount undergoing glomerular filtration (8.4+/-2.0 pmol/min), the renal extraction of C-terminal GLP-1 (9.0+/-1.1 pmol/min), exceeded the amount which could be accounted for by glomerular filtration (4.2+/-0.5 pmol/min, p<0.0005). CONCLUSIONS/INTERPRETATION: In addition to an increased resistance to enzymatic degradation, the increased stability of exendin-4 is the result of reduced differential organ extraction compared to GLP-1. The data suggest that in the anaesthetised pig, extraction occurs only in the kidney and can be fully accounted for by glomerular filtration.

Anesthesia↗

Evaluation of Tc-99m-tetrofosmin single-photon emission computed tomography for detection of chronic exertional compartment syndrome of the leg.

Chronic exertional compartment syndrome (CECS) of the leg is a common, painful condition related to exercise and associated with increased muscle compartment pressure (CP). Invasive methods are currently the method of choice for diagnosing the condition. We investigated the use of Tc-99m-tetrofosmin perfusion single-photon emission computed tomography (SPECT) as a diagnostic tool compared with the gold standard, muscle CP measurement. In 14 subjects perfusion SPECT and CP were measured before and immediately after exercise leading to pain in the lower legs. Six subjects had increased pressures indicating the presence of CECS. In three (50%) of these muscular hypoperfusion was observed by perfusion SPECT. In eight subjects with normal CPs SPECT suggested muscular hypoperfusion. Because of the low diagnostic rates, sensitivity 50% and specificity 63%, Tc-99m-tetrofosmin perfusion SPECT seems not to be a useful method for diagnosing CECS.

Adult↗

More on RotaShield and intussusception: the role of age at the time of vaccination.

BACKGROUND: RotaShield, a vaccine intended to prevent severe rotavirus diarrhea, was withdrawn in July 1999, 9 months after it became available in the United States, because of a temporal association with intussusception events that occurred in vaccinated infants. We explore here the effect of age on the risk of intussusception. METHODS: We reanalyzed a case-control database of the Centers for Disease Control and Prevention by use of a 21-day window, to define vaccine-associated events. We obtained data on vaccine use from the National Immunization Survey and estimated the age-stratified background incidence of intussusception by use of Healthcare Cost and Utilization Project data. We combined these data to estimate how absolute risk varies with age and to model the projected population-attributable risk associated with 3 different vaccination schedules. RESULTS: We found that the incidence of intussusception associated with the first dose of vaccine increased with age. Infants > or = 90 days old accounted for 80% of cases of intussusception associated with a first dose but had received only 38% of first doses. Modeling of the recommended schedule of vaccination at ages 2, 4, and 6 months projected 1 intussusception event/11,000-16,000 vaccine recipients; modeling of a 2-dose schedule beginning in the neonatal period projected 1 intussusception event/38,000-59,000 vaccine recipients. CONCLUSIONS: The practice of initiating immunization after age 90 days, which we call "catch-up" vaccination, contributed disproportionately to the occurrence of intussusception associated with the use of RotaShield. A fully implemented 2-dose vaccination schedule begun during the neonatal period would lead to, at most, a 7% increase in the incidence of intussusception above the annual background incidence.

Age Factors↗

Postprandial triacylglycerol uptake in the legs is increased during exercise and post-exercise recovery.

Six young, healthy male subjects were each studied in two experiments: (1) during resting conditions before and for 360 min after a meal (54% of energy as carbohydrate, 30% of energy as lipid, and 16% of energy as protein) comprising 25% of their total daily energy intake (M-->R); and (2) while exercising on a cycle ergometer for 60 min at 50% of the peak oxygen consumption commencing 60 min after the meal (M-->E) and then for another 240 min. Regional metabolism was measured by Fick's Principle in a leg and in the splanchnic tissue. The combination of food intake and exercise led to increased plasma triacylglycerol (TAG) uptake and clearance in the exercising legs immediately and for at least 4 h post-exercise, while food intake per se did not change leg plasma TAG uptake or clearance for up to 6 h. It is hypothesized that the effect of exercise on leg plasma TAG metabolism is a result of capillary recruitment leading to exposure of the plasma lipoprotein particles to a larger amount of active LPL. In spite of the increased TAG uptake in the exercising legs the arterial plasma TAG concentration had a tendency to increase faster during exercise after a meal than during rest, but it also decreased faster implying that the total lipaemic response was the same whether exercise was performed or not. The amount of lipid taken up in the legs was higher than could be accounted for by whole body lipid oxidation during post-exercise recovery, indicating accumulation of lipid in skeletal muscle in this period. Neither food intake alone nor the combination of food and exercise affected the splanchnic net balance of TAG. Finally, there is an additive effect of exercise and food intake on splanchnic net glucose balance.

Adult↗

Inter- and intralaboratory variation of in vitro diffusion cell measurements: an international multicenter study using quasi-standardized methods and materials.

In vitro measurements of skin absorption are an increasingly important aspect of regulatory studies, product support claims, and formulation screening. However, such measurements are significantly affected by skin variability. The purpose of this study was to determine inter- and intralaboratory variation in diffusion cell measurements caused by factors other than skin. This was attained through the use of an artificial (silicone rubber) rate-limiting membrane and the provision of materials including a standard penetrant, methyl paraben (MP), and a minimally prescriptive protocol to each of the 18 participating laboratories. "Standardized" calculations of MP flux were determined from the data submitted by each laboratory by applying a predefined mathematical model. This was deemed necessary to eliminate any interlaboratory variation caused by different methods of flux calculations. Average fluxes of MP calculated and reported by each laboratory (60 +/- 27 microg cm(-2) h(-1), n = 25, range 27-101) were in agreement with the standardized calculations of MP flux (60 +/- 21 microg cm(-2) h(-1), range 19-120). The coefficient of variation between laboratories was approximately 35% and was manifest as a fourfold difference between the lowest and highest average flux values and a sixfold difference between the lowest and highest individual flux values. Intralaboratory variation was lower, averaging 10% for five individuals using the same equipment within a single laboratory. Further studies should be performed to clarify the exact components responsible for nonskin-related variability in diffusion cell measurements. It is clear that further developments of in vitro methodologies for measuring skin absorption are required.

Clinical Laboratory Techniques↗

The combined effects of exercise and food intake on adipose tissue and splanchnic metabolism.

Seven young, healthy male subjects were each studied in two separate experiments. (1) Subjects exercised for 60 min at 55% of peak oxygen consumption in the fasted state ending 30 min before a meal (60% of energy as carbohydrate, and 20% of energy as lipid and protein each) comprising 25% of the total daily energy intake, and were then studied for another 150 min postprandially during rest (E-->M). (2) One hour after a similar meal, subjects exercised for 60 min and were then studied for another 180 min postexercise during rest (M-->E). Regional adipose tissue and splanchnic tissue metabolism were measured by Fick's Principle. Food intake before exercise reduced whole-body lipid combustion during exercise to about 50% of the combustion rate found during exercise in the fasted state. The increase in subcutaneous, abdominal adipose tissue lipolysis during exercise was not influenced by preexercise food intake, while the fatty acid mobilization was increased by only 1.5-fold during postprandial exercise compared to a fourfold increase during exercise in the fasted state. During exercise, catecholamine concentrations increased similarly in the fasted and the postprandial state, while the insulin concentration was twofold higher postprandially. These results indicate that the increase in catecholamine concentrations during exercise is a more important determinant of the adipose tissue lipolytic rate than the decrease in insulin concentration. Furthermore, food intake either 30 min after or 1 h before exercise prevents the postexercise increase in adipose tissue glycerol and fatty acid release which normally takes place in fasting subjects at least up to 2.5 h postprandially. Postprandial exercise led to a faster increase in postprandial lipaemia. This could not be accounted for by changes in the regional splanchnic tissue or adipose tissue triacylglycerol metabolism. Exercise was able to increase hepatic glucose production irrespective of food intake before exercise. It is concluded that exercise performed in the fasted state shortly before a meal leads to a more favourable lipid metabolism during and after exercise than exercise performed shortly after a meal.

Adipose Tissue↗

The effect of exercise on regional adipose tissue and splanchnic lipid metabolism in overweight type 2 diabetic subjects.

AIMS/HYPOTHESIS: To test the hypothesis that adipose tissue lipolysis is enhanced in patients with Type 2 diabetes mellitus, we examined the effect of exercise on regional adipose tissue lipolysis and fatty acid mobilisation and measured the acute effects of exercise on the co-ordination of adipose tissue and splanchnic lipid metabolism. METHODS: Abdominal, subcutaneous adipose tissue and splanchnic lipid metabolism were studied by conducting measurements of arterio-venous concentrations and regional blood flow in six overweight Type 2 diabetic subjects before, during and after exercise. RESULTS: Exercise induced an increase in adipose tissue lipolysis and fatty acid release. However, the increase in adipose tissue blood flow was small, limiting fatty acid mobilisation from this tissue. Some of the fatty acids were released in excess in the post-exercise phase. The splanchnic fatty acid uptake was unchanged during the experiment but splanchnic ketogenesis increased in the post-exercise phase. The arterial glucose concentration decreased during exercise and continued to decrease afterwards, indicating an imbalance between splanchnic glucose production and whole-body glucose utilisation. CONCLUSIONS/INTERPRETATION: Regional subcutaneous, abdominal adipose tissue lipolysis is no higher in patients with Type 2 diabetes than in young, healthy subjects. Exercise stimulates adipose tissue lipolysis, but due to an insufficient increase in blood flow, a high fraction of the fatty acids liberated by lipolysis cannot be released to the blood. Splanchnic glucose release is smaller than whole-body glucose utilisation during exercise and post-exercise recovery.

Adipose Tissue↗

Does the pattern of venous insufficiency influence healing of venous leg ulcers after skin transplantation?

AIMS: this study aimed to investigate the influence of venous insufficiency on results in venous leg ulcers treated with ulcer excision, meshed split-skin transplantation and correction of superficial venous insufficiency in the wound area. DESIGN: retrospective cohort study. SETTING: Copenhagen Wound Healing Center. METHODS: in 113 patients with venous leg ulceration, examined preoperatively with colour Duplex scanning (CDS), prognostic factors of healing and recurrence within 1 year were analysed using logistic regression. RESULTS: cumulative 1-year healing rate was 65% (73 patients) and 13 (12%) had recurrence of ulceration 1 year postoperatively. Initial ulcer size (OR: 0.97(95% CI: 0.96-0.99)), minor local superficial venous surgery (OR: 2.38 (95% CI: 1.04-5.46)), sufficient popliteal vein (2.97 (1.05-8.42)) and non-compliance with compression therapy (OR: 0.27 (95% CI: 0.11-0.71)) influenced the prognosis of healing positively. No statistically significant differences in healing and recurrence between patients with isolated superficial and mixed superficial/deep venous insufficiency was found. CONCLUSION: non-healing venous leg ulcers can be treated with ulcer excision, meshed split-skin transplantation and correction of superficial venous insufficiency in the wound area with beneficial results irrespective of underlying pattern of venous insufficiency as determined by CDS.

Aged↗

The effect of topically applied salicylic compounds on serotonin-induced scratching behaviour in hairless rats.

There is a strong need for antipruritic substances for treating itch in clinical dermatology. In one recent human study, topically applied acetylsalicylic acid has been described to rapidly decrease histamine-induced itch. We have established a model for periferally elicited pruritus by injecting serotonin into the rostral back area (neck) in rats. Using this model, we aimed to investigate the antipruritic potential of four different salicylic compounds, which all possess different skin penetration characteristics. Eighteen rats were studied for 6 weeks. Prior to serotonin injections (2 mg/ml, 50 micro l), 10 micro l of test substances was applied to a circular area 18 mm in diameter. The four substances were salicylic acid, butyl salicylate, diethylamine salicylate and salicylamide, all solubilized in dimethyl isosorbide to a concentration of 5% w/w. Diethylamine salicylate and salicylamide were previously shown to be slowly absorbed through rat skin in contrast to salicylic acid and butyl salicylate. After serotonin injections, scratching was monitored by video recording for 1.5 h. Compared with the vehicle, a lower number of scratch sequences were seen when diethylamine salicylate (P < 0.001) and salicylamide (P = 0.005) had been applied. The numbers of scratch sequences were lower with diethylamine salicylate and salicylamide than with the vehicle throughout the 1.5-h study period. We conclude that topical application of diethylamine salicylate and salicylamide could suppress serotonin-induced scratching in rats. The antipruritic effect seems to be related to the slow drug release of the two substances. The results may be clinically relevant as serotonin induces itch in humans.

Administration, Topical↗

Effect of rotavirus vaccination programme on trends in admission of infants to hospital for intussusception.

BACKGROUND: Studies have reported a temporal association between a first dose of rotavirus vaccine (Rotashield) and infant intussusception. We investigated the effect of Rotashield vaccination use on intussusception admissions in ten US states. METHODS: We analysed electronic databases containing 100% hospital discharge records for 1993-99 from ten US states, where an estimated 28% of the birth cohort had received Rotashield (based on manufacturer's net sales data). We examined records of infants admitted to hospital (<365 days old) with any mention of intussusception (International Classification of Diseases, ninth revision, clinical modification code 560.0). Excess admissions for intussusception during the period of Rotashield availability (October 1998 to June 1999) were estimated by direct comparison with the corresponding period of October 1997 to June 1998 (before Rotashield was available) and with adjustment for secular trends during 1993-98 by Poisson regression. FINDINGS: Hospital admission for intussusception among infants younger than 365 days of age during the Rotashield period compared with previously was 4% lower (10 cases) by direct comparison and 10% lower (27 cases) by trend comparison, corresponding to a negative population attributable risk. Among infants aged 45-210 days (target age range for a first Rotashield dose), we estimated an increase in intussusception admissions of 1% (one excess admission) by direct comparison and 4% (4.6 excess admissions) by trend comparison, corresponding to a population attributable risk range of one excess admission in 66000-302000. INTERPRETATION: We found no evidence of increased infant intussusception admissions during the period of Rotashield availability. The total intussusception admission risk attributable to Rotashield was substantially lower than previous estimates based on studies focusing on the immediate postvaccination weeks.

Case-Control Studies↗

Global trends in resistance to antituberculosis drugs. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance.

BACKGROUND: Data on global trends in resistance to antituberculosis drugs are lacking. METHODS: We expanded the survey conducted by the World Health Organization and the International Union against Tuberculosis and Lung Disease to assess trends in resistance to antituberculosis drugs in countries on six continents. We obtained data using standard protocols from ongoing surveillance or from surveys of representative samples of all patients with tuberculosis. The standard sampling techniques distinguished between new and previously treated patients, and laboratory performance was checked by means of an international program of quality assurance. RESULTS: Between 1996 and 1999, patients in 58 geographic sites were surveyed; 28 sites provided data for at least two years. For patients with newly diagnosed tuberculosis, the frequency of resistance to at least one antituberculosis drug ranged from 1.7 percent in Uruguay to 36.9 percent in Estonia (median, 10.7 percent). The prevalence increased in Estonia, from 28.2 percent in 1994 to 36.9 percent in 1998 (P=0.01), and in Denmark, from 9.9 percent in 1995 to 13.1 percent in 1998 (P=0.04). The median prevalence of multidrug resistance among new cases of tuberculosis was only 1.0 percent, but the prevalence was much higherin Estonia (14.1 percent), Henan Province in China (10.8 percent), Latvia (9.0 percent), the Russian oblasts of Ivanovo (9.0 percent) and Tomsk (6.5 percent), Iran (5.0 percent), and Zhejiang Province in China (4.5 percent). There were significant decreases in multidrug resistance in France and the United States. In Estonia, the prevalence in all cases increased from 11.7 percent in 1994 to 18.1 percent in 1998 (P<0.001). CONCLUSIONS: Multidrug-resistant tuberculosis continues to be a serious problem, particularly among some countries of eastern Europe. Our survey also identified areas with a high prevalence of multidrug-resistant tuberculosis in such countries as China and Iran.

Antitubercular Agents↗

The Japanese experience with vaccinating schoolchildren against influenza.

BACKGROUND: Influenza epidemics lead to increased mortality, principally among elderly persons and others at high risk, and in most developed countries, influenza-control efforts focus on the vaccination of this group. Japan, however, once based its policy for the control of influenza on the vaccination of schoolchildren. From 1962 to 1987, most Japanese schoolchildren were vaccinated against influenza. For more than a decade, vaccination was mandatory, but the laws were relaxed in 1987 and repealed in 1994; subsequently, vaccination rates dropped to low levels. When most schoolchildren were vaccinated, it is possible that herd immunity against influenza was achieved in Japan. If this was the case, both the incidence of influenza and mortality attributed to influenza should have been reduced among older persons. METHODS: We analyzed the monthly rates of death from all causes and death attributed to pneumonia and influenza, as well as census data and statistics on the rates of vaccination for both Japan and the United States from 1949 through 1998. For each winter, we estimated the number of deaths per month in excess of a base-line level, defined as the average death rate in November. RESULTS: The excess mortality from pneumonia and influenza and that from all causes were highly correlated in each country. In the United States, these rates were nearly constant over time. With the initiation of the vaccination program for schoolchildren in Japan, excess mortality rates dropped from values three to four times those in the United States to values similar to those in the United States. The vaccination of Japanese children prevented about 37,000 to 49,000 deaths per year, or about 1 death for every 420 children vaccinated. As the vaccination of schoolchildren was discontinued, the excess mortality rates in Japan increased. CONCLUSIONS: The effect of influenza on mortality is much greater in Japan than in the United States and can be measured about equally well in terms of deaths from all causes and deaths attributed to pneumonia or influenza. Vaccinating schoolchildren against influenza provides protection and reduces mortality from influenza among older persons.

Aged↗

Leptin levels are associated with fat oxidation and dietary-induced weight loss in obesity.

OBJECTIVE: To examine the relationship between fasting plasma leptin and 24-hour energy expenditure (EE), substrate oxidation, and spontaneous physical activity (SPA) in obese subjects before and after a major weight reduction compared with normal weight controls. To test fasting plasma leptin, substrate oxidations, and SPA as predictive markers of success during a standardized weight loss intervention. RESEARCH METHODS AND PROCEDURES: Twenty-one nondiabetic obese (body mass index: 33.9 to 43.8 kg/m(2)) and 13 lean (body mass index: 20.4 to 24.7 kg/m(2)) men matched for age and height were included in the study. All obese subjects were reexamined after a mean weight loss of 19.2 kg (95% confidence interval: 15.1-23.4 kg) achieved by 16 weeks of dietary intervention followed by 8 weeks of weight stability. Twenty-four-hour EE and substrate oxidations were measured by whole-body indirect calorimetry. SPA was assessed by microwave radar. RESULTS: In lean subjects, leptin adjusted for fat mass (FM) was correlated to 24-hour EE before (r = -0.56, p < 0.05) but not after adjustment for fat free mass. In obese subjects, leptin correlated inversely with 24-hour and resting nonprotein respiratory quotient (r = -0.47, p < 0.05 and r = -0.50, p < 0.05) both before and after adjustments for energy balance. Baseline plasma leptin concentration, adjusted for differences in FM, was inversely related to the size of weight loss after 8 weeks (r = -0.41, p = 0.07), 16 weeks (r = -0.51, p < 0.05), and 24 weeks (r = -0.50, p < 0.05). DISCUSSION: The present study suggests that leptin may have a stimulating effect on fat oxidation in obese subjects. A low leptin level for a given FM was associated with a greater weight loss, suggesting that obese subjects with greater leptin sensitivities are more successful in reducing weight.

Absorptiometry, Photon↗

Recovery of autonomic nervous activity after myocardial infarction demonstrated by short-term measurements of SDNN.

OBJECTIVE: Heart rate variability (HRV) has been demonstrated to be a risk factor after acute myocardial infarction (AMI). In the present study serial measurement of SDNN (standard deviation of the mean of qualified NN-interval) in short intervals was used to assess HRV changes after AMI, and determine the role of these as independent risk factors compared to clinical, arrhythmic, ischemic and anamnestic variables. Measurements from a normal healthy middle-aged male population were used as reference (n = 63). METHODS: SDNN from a five-minute period during day and night-time, respectively, was examined in 103 patients 1 week (n = 54), 1 month (n = 72) and 12-16 months (n = 54) after infarction. RESULTS: Day SDNN did not change during one-and-a-half years after AMI, and was significantly reduced compared with healthy males. Night SDNN, low after 1 week, with recovery 1 month after AMI, was significantly reduced compared with healthy males early, but not late after AMI. Thus, the study indicated during day-time a continuous abnormal sympathetic preponderance in the course of 16 months after AMI, and during night-time a gradual recovery of parasympathetic preponderance beginning early after AMI. CONCLUSION: One week after AMI day-time SDNN of <30 ms, and night-time SDNN of < 18 ms, age > or =60 years, and myocardial ischemia (Holter monitoring) were independent predictors of 9 years' mortality. One and 12-16 months after AMI reduced day and night-time SDNN had no prognostic implication.

Aged↗

Stimulation of splanchnic glucose production during exercise in humans contains a glucagon-independent component.

To determine the importance of basal glucagon to the stimulation of net splanchnic glucose output (NSGO) during exercise, seven healthy males performed cycle exercise during a pancreatic islet cell clamp. In one group (BG), glucagon was replaced at basal levels and insulin was adjusted to achieve euglycemia. In another group (GD), only insulin was replaced at the identical rate used in BG, and basal glucagon was not replaced. Exogenous glucose infusion was necessary to maintain euglycemia during exercise in BG and during rest and exercise in GD. Arterial glucagon was at least twofold greater in BG than in GD throughout the pancreatic islet cell clamp. Although basal NSGO remained stable in BG (2.5 +/- 0.5 mg x kg(-1) x min(-1)), basal NSGO dropped by 70% in GD (0.7 +/- 0.3 mg. kg(-1) x min(-1)). NSGO was also greater in BG than in GD at 10 min of moderate exercise, most likely due to the residual effect of basal glucagon replacement. However, NSGO increased slightly and remained similar throughout the remainder of moderate and heavy exercise in BG and GD. Therefore, a mechanism independent of changes in pancreatic hormones and/or the level of glycemia contributes toward modest stimulation of NSGO during moderate and heavy exercise.

Adult↗

In vivo human lipolytic activity in preperitoneal and subdivisions of subcutaneous abdominal adipose tissue.

We studied eight normal-weight male subjects to examine whether the lipolytic rate of deep subcutaneous and preperitoneal adipose tissues differs from that of superficial abdominal subcutaneous adipose tissue. The lipolytic rates in the superficial anterior and deep posterior subcutaneous abdominal adipose tissues and in the preperitoneal adipose tissue in the round ligament were measured by microdialysis and (133)Xe washout under basal, postabsorptive conditions and during intravenous epinephrine infusion (0.15 nmol. kg(-1). min(-1)). Both in the basal state and during epinephrine stimulation, the superficial subcutaneous adipose tissue had higher interstitial glycerol concentrations than the two other depots. Similarly, the calculated glycerol outputs from the superficial depot were significantly higher than those from the deep subcutaneous and the preperitoneal depots. Thus, it is concluded that the lipolytic rate of the superficial subcutaneous adipose tissue on the anterior abdominal wall is higher than that of the deep subcutaneous adipose tissue on the posterior abdominal wall and that of the preperitoneal adipose tissue in the round ligament.

Abdomen↗

Splanchnic blood flow and hepatic glucose production in exercising humans: role of renin-angiotensin system.

The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O(2) consumption (VO(2 max)) followed by 30 min at 70% VO(2 max) either with [angiotensin-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an approximately 20-fold increase (P < 0.001) in ANG II levels in the control group (5.4 +/- 1.0 to 102.0 +/- 25.1 pg/ml), whereas this response was blunted during ACE blockade (8.1 +/- 1.2 to 13.2 +/- 2.4 pg/ml) and in response to an orthostatic challenge performed postexercise. Apart from lactate and cortisol, which were higher in the ACE-blockade group vs. the control group, hormones, metabolites, VO(2), and RER followed the same pattern of changes in ACE-blockade and control groups during exercise. Splanchnic blood flow (at rest: 1.67 +/- 0.12, ACE blockade; 1.59 +/- 0.18 l/min, control) decreased during moderate exercise (0.78 +/- 0.07, ACE blockade; 0.74 +/- 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 +/- 0.06, ACE blockade; 0.68 +/- 0.10 mmol/min, control) increased during moderate exercise (1.97 +/- 0.29, ACE blockade; 1.91 +/- 0.41 mmol/min, control). Refuting a major role of the RAS for these responses, no differences in the pattern of change of splanchnic blood flow and splanchnic glucose production were observed during ACE blockade compared with controls. This study demonstrates that the normal increase in ANG II levels observed during prolonged exercise in humans does not play a major role in the regulation of splanchnic blood flow and glucose production.

Adrenocorticotropic Hormone↗

Post-exercise adipose tissue and skeletal muscle lipid metabolism in humans: the effects of exercise intensity.

One purpose of the present experiments was to examine whether the relative workload or the absolute work performed is the major determinant of the lipid mobilization from adipose tissue during exercise. A second purpose was to determine the co-ordination of skeletal muscle and adipose tissue lipid metabolism during a 3 h post-exercise period. Six subjects were studied twice. In one experiment, they exercised for 90 min at 40% of maximal O2 consumption (VO2,max) and in the other experiment they exercised at 60% VO2,max for 60 min. For both experiments, catheters were inserted in an artery, a subcutaneous abdominal vein and a femoral vein. Adipose tissue metabolism and skeletal muscle (leg) metabolism were measured using Fick's principle. The results show that the lipolytic rate in adipose tissue during exercise was the same in each experiment. Post-exercise, there was a very fast decrease in lipolysis, but it began to increase about 1 h post-exercise and remained elevated for the following 2 h. The increase in post-exercise non-esterified fatty acid (NEFA) mobilization was greater after 60% exercise than after 40 % exercise. It is concluded that the lipolytic rate in abdominal subcutaneous adipose tissue during exercise is the same whether the relative workload is 40% or 60% of maximum. Post-exercise, there is a substantial lipid mobilization from adipose tissue and only a small fraction of this is taken up in the lower extremities. This leaves a substantial amount of NEFAs for either NEFA/TAG (triacylglycerol) recirculation post-exercise or immediate oxidation.

Adipose Tissue↗