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Biomedical subjects

J Wahren

Publications and source records attributed to J Wahren.

At least 127 records · Page 7Linked to original sources
PubMed1989

Meal-induced thermogenesis in obese patients before and after weight reduction.

The purpose of this study was to find out whether human obesity is associated with a diminished meal-induced thermogenesis and, if so, to what extent this response is influenced by weight reduction. Ten obese subjects (body mass index 42 +/- 2) and 10 age- and sex-matched non-obese volunteers were studied with continuous indirect calorimetry in the basal state and after the ingestion of a standardized test meal. Six obese subjects (body mass index 44 +/- 2) were examined on two occasions, once before and once after gastric banding and an average weight reduction of 18 +/- 3 kg. Basal oxygen uptake and energy expenditure were 30% (P less than 0.001) greater in the obese subjects compared to non-obese controls. After the meal, pulmonary oxygen uptake and energy expenditure increased rapidly and reached a relatively constant level after 60 min; for pulmonary oxygen uptake the average rise above basal was less in the obese (17.7 +/- 1.6%) than the non-obese (27.8 +/- 1.9%, P less than 0.001); the increase in energy expenditure was 18.5 +/- 1.7% in obese and 30.8 +/- 2.1% in non-obese subjects (P less than 0.001). After weight reduction, oxygen uptake and energy expenditure in the basal state were 20% lower (P less than 0.05) than before weight reduction. The average post-prandial increase in oxygen uptake was greater after weight reduction (24.8 +/- 2.0%) than before (16.7 +/- 1.6%, P less than 0.001). Corresponding values for energy expenditure were 27.2 +/- 2.2 and 18.2 +/- 2.2% (P less than 0.001). It is concluded that: (1) the thermogenic response to a mixed meal is lower in obese compared to non-obese individuals; and, (2) this impaired response is partly normalized after weight reduction. These findings suggest that a diminished meal-induced thermogenesis is a secondary phenomenon rather than a primary pathogenic factor in human obesity.

Adult↗
PubMed1989

Splanchnic and renal exchange of infused fructose in insulin-deficient type 1 diabetic patients and healthy controls.

Fructose raises blood glucose and lactate levels in normal as well as diabetic man, but the tissue origin (liver and/or kidney) of these responses and the role of insulin in determining the end products of fructose metabolism have not been fully established. Splanchnic and renal substrate exchange was therefore examined during intravenous infusion of fructose or saline in six insulin-deficient type I diabetics who fasted overnight and in five healthy controls. Fructose infusion resulted in similar arterial concentrations and regional uptake of fructose in the two groups. Splanchnic glucose output increased threefold in the diabetics but remained unchanged in controls in response to fructose infusion, and the arterial glucose concentration rose more in diabetics (+5.5 mmol/liter) than in controls (+0.5 mmol/liter). Splanchnic uptake of both lactate and pyruvate increased twofold in response to fructose infusion in the diabetics. In contrast, a consistent splanchnic release of both lactate and pyruvate was seen during fructose infusion in controls. In diabetics fructose-induced hyperglycemia was associated with no net renal glucose exchange, while there was a significant renal glucose production during fructose infusion in the controls. In both groups fructose infusion resulted in renal output of lactate and pyruvate. In the diabetics this release corresponded to the augmented uptake by splanchnic tissues. In two diabetic patients given insulin infusion, all responses to fructose infusion were normalized. Fructose infusion in diabetics did not influence either splanchnic ketone body production or its relationship to splanchnic FFA inflow. We conclude that in insulin-deficient, mildly ketotic type I diabetes, (a) both the liver, by virtue of lactate, pyruvate, and fructose-derived gluconeogenesis, and the kidneys , by virtue of fructose-derived lactate and pyruvate production, contribute to fructose-induced hyperglycemia; (b) outcome of hepatic fructose metabolism; and (c) fructose does not exert an antiketogenic effect. These data suggest that while total fructose metabolism is not altered in diabetics, intermediary hepatic fructose metabolism is dependent on the presence of insulin.

Adult↗
PubMed1989

Effects of pancreas transplantation on metabolic and hormonal profiles in IDDM patients.

The diurnal patterns of relevant metabolites and hormones in five pancreas-kidney-transplanted patients (aged 36 +/- 2 yr, mean +/- SD) with insulin-dependent diabetes mellitus (IDDM) were compared with those in five kidney-transplanted nondiabetic patients (aged 28 +/- 2 yr). The groups were matched for body mass and current dose and type of immunosuppressive treatment. The serum creatinine levels did not differ between the two study groups, but the serum urea level in the nondiabetic patients was slightly but significantly higher than in the diabetic patients. In the pancreas-kidney-transplanted group the investigation was performed 8-47 mo posttransplantation; in the kidney-transplanted nondiabetic patients, 12-18 mo posttransplantation. The mean 24-h levels and rhythms of blood glucose, free fatty acid, 3-hydroxybutyrate, and alanine did not differ between the groups. The mean 24-h levels of blood lactate and glycerol were moderately but significantly higher in the pancreas-kidney-transplanted diabetic patients. At fasting, the level of serum immunoreactive insulin was more than twice as high in the pancreas-kidney-transplanted patients, whereas the plasma C-peptide levels did not differ significantly between the two groups. The meal-induced increases in serum insulin as well as in the plasma C-peptide levels were more marked in the pancreas-kidney-transplanted patients. The findings suggest that the hyperinsulinemia in these patients was due to both the systemic delivery of insulin and an increase in insulin resistance, the latter being particularly apparent in the postprandial phase.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1988

Influence of hyperinsulinaemia on intracellular amino acid levels and amino acid exchange across splanchnic and leg tissues in uraemia.

1. To examine whether insulin resistance in uraemia extends to amino acid metabolism, the effect of physiological hyperinsulinaemia on plasma amino acid concentrations was studied in 17 chronically uraemic and 28 healthy subjects by using the euglycaemic insulin clamp technique. 2. In six uraemic and seven control subjects, splanchnic and leg exchange of amino acids was quantified with hepatic and femoral venous catheterization, and in five uraemic and eight control subjects intracellular free amino acid concentrations were determined in muscle tissue obtained by needle biopsy. 3. In response to hyperinsulinaemia the plasma concentrations of all amino acids except alanine decreased by 10-50% in both uraemic and control subjects. Splanchnic alanine uptake declined by 20% and leg amino acid release tended to decrease in both groups. 4. The intracellular levels of all measured amino acids except alanine fell significantly and to a similar extent in uraemic and control subjects. 5. These results indicate that insulin-mediated alterations in regional amino acid exchange and in plasma and intracellular amino acid concentrations are similar in uraemic and control subjects. 6. It is concluded that tissue insensitivity to insulin in uraemia does not extend to uptake or release of amino acids and that resistance to insulin can be selective in its effect on different metabolic functions.

Adult↗
PubMed1988

[Results following anterior levator-plasty].

In this study we report about 172 patients who underwent modified anterior repair in the time from october 1983 up to april 1985 because of vaginal prolapse and/or incontinence. 125 patients could be examined clinically, in the middle 14.2 months after operation. In 64% the modified anterior repair was combined with a colporrhaphia anterior and hysterectomy, and in 20% a colporrhaphia posterior was made additionally. Dehiscence of the anterior vaginal wall occurred in 19.2%, severe pelvic infections in 8.8%. Because of bleeding complications a chirurgical intervention was necessary in 5.6%. A descent of the anterior vaginal wall was seen in 30.4%, 76.8% of the women developed a descent of the posterior vaginal wall, and 8% a stenosis of the vagina. Problems at sexual intercourse were frequent, followed by pain in the lower abdomen. The principle of the operation is presented including the changed anatomy. Many of the adverse effects can be understood and the necessity of prophylaxis of a descensus of posterior vaginal wall was described.

Adult↗
PubMed1988

Pentose pathway in human liver.

[1-14C]Ribose and [2-14C]glucose were given to normal subjects along with glucose loads (1 g per kg of body weight) after administration of diflunisal and acetaminophen, drugs that are excreted in urine as glucuronides. Distributions of 14C were determined in the carbons of the excreted glucuronides and in the glucose from blood samples drawn from hepatic veins before and after glucagon administration. Eighty percent or more of the 14C from [1-14C]ribose incorporated into the glucuronic acid moiety of the glucuronides was in carbons 1 and 3, with less than 8% in carbon 2. In glucuronic acid from glucuronide excreted when [2-14C]glucose was given, 3.5-8.1% of the 14C was in carbon 1, 2.5-4.3% in carbon 3, and more than 70% in carbon 2. These distributions are in accord with the glucuronides sampling the glucose unit of the glucose 6-phosphate pool that is a component of the pentose pathway and is intermediate in glycogen formation. It is concluded that the glucuronic acid conjugates of the drugs can serve as a noninvasive means of sampling hepatic glucose 6-phosphate. In human liver, as in animal liver, the classical pentose pathway functions, not the L-type pathway, and only a small percentage of the glucose is metabolized via the pathway.

Acetaminophen↗
PubMed1988

Quantification of the pathways followed in hepatic glycogen formation from glucose.

Quantitative contributions of the direct and indirect pathways to liver glycogen formation from a glucose load have been estimated from 1) the distribution of label in glycogen formed from specifically carbon-labeled loads of glucose, 2) the specific activity of the glycogen compared with that of the circulating glucose, 3) the 3H:14C ratios in glycogen formed from loads specifically labeled with 3H and 14C, 4) the incorporation of 3H from 3H2O into the glycogen, and 5) the balance of glucogenic substrates across the splanchnic bed. A number of assumptions are made in the use of each of these methods. Estimates have been made for animals and humans fasted overnight or longer. Results obtained with the different methods are compared. Under these conditions, the contribution of the pathways appears to be determined by the size of the load, with larger contributions of the indirect pathway occurring with smaller loads.

Animals↗
PubMed1988

Influence of carnitine supplementation on muscle substrate and carnitine metabolism during exercise.

We examined 1) the effect of L-carnitine supplementation on free fatty acid (FFA) utilization during exercise and 2) exercise-induced alterations in plasma levels and skeletal muscle exchange of carnitine. Seven moderately trained human male subjects serving as their own controls participated in two bicycle exercise sessions (120 min, 50% of VO2max). The second exercise was preceded by 5 days of oral carnitine supplementation (CS; 5 g daily). Despite a doubling of plasma carnitine levels, with CS, there were no effects on exercise-induced changes in arterial levels and turnover of FFA, the relation between leg FFA inflow and FFA uptake, or the leg exchange of other substrates. Heart rate during exercise after CS decreased 7-8%, but O2 uptake was unchanged. Exercise before CS induced a fall from 33.4 +/- 1.6 to 30.8 +/- 1.0 (SE) mumol/l in free plasma carnitine despite a release (2.5 +/- 0.9 mumol/min) from the leg. Simultaneously, acylated plasma carnitine rose from 5.0 +/- 1.0 to 14.2 +/- 1.4 mumol/l, with no evidence of leg release. Consequently, total plasma carnitine increased. We concluded that in healthy subjects CS does not influence muscle substrate utilization either at rest or during prolonged exercise and that free carnitine released from muscle during exercise is presumably acylated in the liver and released to plasma.

3-Hydroxybutyric Acid↗
PubMed1987

Blood flow, substrate utilization and heat generation in tissues drained by the azygos vein in man.

The present study was undertaken to examine the blood flow, heat generation and substrate utilization in tissues drained by the azygos vein in healthy subjects. Catheters were inserted percutaneously into the azygos vein and the pulmonary artery in 10 healthy male subjects in the basal, post-absorptive state. Blood flow in the azygos vein was measured by thermodilution technique, blood temperature was recorded in both the azygos vein and the pulmonary artery and blood samples for the determination of oxygen content and substrate concentrations were collected from both vessels repeatedly at timed intervals. Free fatty acid (FFA) exchange was evaluated following the intravenous infusion of 14-C labelled oleic acid. The average azygos vein blood flow was 94 +/- 10 ml/min. The coefficient of variation for the flow determination was 3.6%. The blood temperature in the azygos vein was consistently higher than that in the pulmonary artery, indicating an average calculated net heat production in the tissues of 0.5 W. The oxygen uptake to the tissues drained by the azygos vein amounted to 6 +/- 1 ml/min. Significant amounts of glucose, FFA and ketone bodies were taken up in the azygos area, while both glycerol and FFA were released. The FFA uptake could, if oxidized, account for about half of the oxygen uptake. In conclusion, the findings indicate that, in the basal state, the tissues drained by the azygos vein utilize both glucose and FFA. Heat is generated within the area but the rate of generation is low and can largely be explained by the oxidative metabolism. The findings do not support an important role for brown adipose tissue metabolism in the interscapular region in man.

3-Hydroxybutyric Acid↗
PubMed1987

Quantitation of the pathways of hepatic glycogen formation on ingesting a glucose load.

Diflunisal, 5-(2',4'-difluorophenyl)salicylic acid, excreted in urine as its glucuronide, was given to normal humans (n = 6) along with a glucose load specifically labeled with 14C. Glucuronide excreted by each subject was reduced to its glucoside and glucose from it degraded to yield the distribution of 14 C in its six carbons. Randomization of the 14C from the specifically labeled glucose was taken as a measure of the extent to which glucose was deposited indirectly (i.e., glucose----lactate----glucose----6-P----glycogen), rather than directly (i.e., glucose----glucose-6-P----glycogen). The maximum contribution to glycogen formation by the direct pathway was estimated to be 65 +/- 1%, on the assumption that glucuronide and glycogen are derived from the same hepatic pool of glucose-6-P in liver. Evidence that supports that assumption was obtained by comparing the randomization of 14C in the urinary glucuronide with that in glucose in blood from the hepatic vein of four of the subjects before and after they were given glucagon. Other evidence supporting the assumption was obtained by comparing in two subjects 3H/14C ratios in glucose from hepatic vein blood before and after glucagon administration with that in urinary glucuronide, having labeled the uridine diphosphate (UDP)-glucose in their livers with 14C by giving them 1-[14C]galactose and their circulating glucose with 3H by giving a 5-[3H]glucose-labeled load. It is concluded that glucuronide formation in humans can be used to trace glucose metabolism in the liver, and that in humans the indirect pathway of glucose metabolism is active.

Administration, Oral↗
PubMed1987

Haemodynamic effects of a long-acting somatostatin analogue in patients with liver cirrhosis.

The influence of SMS 201-995 (octreotide, Sandostatin), a long-acting somatostatin analogue, on splanchnic haemodynamics was studied in 15 patients with liver cirrhosis and in 5 healthy individuals before, during, and after 60 min of intravenous SMS infusion (25 and 50 micrograms/h, respectively). No adverse effects of the SMS infusion were seen. In the basal state the estimated hepatic blood flow was 1.04 +/- 0.08 l/min (mean +/- SE) in the patients and 1.62 +/- 0.09 l/min (P less than 0.001) in the controls. At 15 min after the beginning of the infusion the blood flow had already decreased by 15-30% (P less than 0.05-0.01). The reduction was more marked in controls than in patients, and it persisted in both groups during and for 60 min after the infusion. Wedged hepatic venous pressure, measured in the patients, was 20 +/- 2 mmHg in the basal state and 18 +/- 1 mmHg during the infusion (P less than 0.05), and it remained at this level for 60 min after the infusion. Free hepatic venous pressure was unchanged throughout the study. Splanchnic oxygen uptake was similar in the two groups in the basal state and remained unaltered during and after SMS infusion. Both heart rate and arterial systolic and diastolic blood pressure remained unchanged during SMS administration. In summary, SMS infusion results in a fall in hepatic blood flow and a slight but significant decrease in wedged hepatic venous pressure, whereas no effect was noted on the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Increased 24-hour energy expenditure in cigarette smokers.

We studied the effect of smoking on energy expenditure in eight healthy cigarette smokers who spent 24 hours in a metabolic chamber on two occasions, once without smoking and once while smoking 24 cigarettes per day. Diet and physical exercise (30 minutes of treadmill walking) were standardized on both occasions. Physical activity in the chamber was measured by use of a radar system. Smoking caused an increase in total 24-hour energy expenditure (from a mean value [+/- SEM] of 2230 +/- 115 to 2445 +/- 120 kcal per 24 hours; P less than 0.001), although no changes were observed in physical activity or mean basal metabolic rate (1545 +/- 80 vs. 1570 +/- 70 kcal per 24 hours). During the smoking period, the mean diurnal urinary excretion of norepinephrine (+/- SEM) increased from 1.25 +/- 0.14 to 1.82 +/- 0.28 micrograms per hour (P less than 0.025), and mean nocturnal excretion increased from 0.73 +/- 0.07 to 0.91 +/- 0.08 micrograms per hour (P less than 0.001). These short-term observations demonstrate that cigarette smoking increases 24-hour energy expenditure by approximately 10 percent, and that this effect may be mediated in part by the sympathetic nervous system. The findings also indicate that energy expenditure can be expected to decrease when people stop smoking, thereby favoring the gain in body weight that often accompanies the cessation of smoking.

Adult↗
PubMed1986

Long-term physical training in female type 1 (insulin-dependent) diabetic patients: absence of significant effect on glycaemic control and lipoprotein levels.

No objective evidence has been presented to support the beneficial effect of physical training on glycaemic control in Type 1 (insulin-dependent) diabetic patients trained two to three times a week for several months. In the present study we examined the possibility that a daily exercise programme would be more suitable for improving glycaemic control. Thirteen patients completed a 5-month study; 6 were randomized to exercise training (20 min daily bicycle exercise) and 7 served as non-exercising controls. The training resulted in an 8% increase in maximal oxygen uptake (p less than 0.05). No change in glycaemic control occurred during the study period in either group. In addition, serum lipid and lipoprotein levels were followed. Total cholesterol decreased during the study period irrespective of training. No effect was noted on the levels of LDL, VLDL, HDL and HDL2 cholesterol. A significant training effect was obtained in the HDL3 subfraction (-10%, p less than 0.05). Total triglycerides were unchanged, but a decrease in the level of LDL triglycerides was observed with training (-12%, p less than 0.01). It is concluded that, in female Type 1 diabetic patients, daily physical training for several months does not improve glycaemic control and results only in minor changes in serum lipoprotein profiles.

Adult↗
PubMed1986

Splanchnic and leg exchange of free fatty acids in patients with liver cirrhosis.

Splanchnic and leg exchange of free fatty acids (FFA), glycerol and ketone bodies, as well as FFA turnover, were determined in the post-absorptive state in 8 patients with liver cirrhosis and in 6 healthy control subjects. The catheter technique was used together with tracer ([14C]oleate) infusion. The arterial concentrations of FFA, glycerol and ketone bodies were 2-6-fold higher in the patients than in the controls. The FFA turnover was 230% greater in the patients, while the fractional turnover was similar in the two groups. In the splanchnic region as well as in the leg, both FFA uptake and release were increased 2-4-fold in the patients. The fractional uptake of FFA was reduced in both areas, indicating that the augmented uptake was due to the high circulating FFA levels alone. The splanchnic production of ketone bodies was four times higher in the patients than in the controls (295 +/- 30 vs 87 +/- 11 mumol/min). The fraction of FFA converted to ketone bodies was greater (42 +/- 6 vs 20 +/- 5%, P less than 0.05), indicating that the accelerated ketone body production was a combined effect of raised FFA uptake and altered intrahepatic metabolism of FFA. The splanchnic production of glucose was reduced by approximately 50% in the patients, while the uptake of glycerol was augmented. The leg uptake of 3-hydroxybutyrate was increased 300% and the release of glycerol was 200% greater in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1986

Muscle ammonia and amino acid metabolism during dynamic exercise in man.

The effect of dynamic exercise on muscle and blood ammonia (NH3) and amino acid contents has been investigated. Eight healthy men cycled at 50% and 97% of maximal oxygen uptake for 10 min and 5.2 min (to fatigue), respectively. Biopsies (quadriceps femoris muscle), arterial and femoral venous blood samples were obtained at rest and during exercise. Muscle NH3 at rest and after submaximal exercise was (means +/- SE) 0.5 +/- 0.1 mmol/kg dry muscle (d.m.) and increased to 4.1 +/- 0.5 mmol/kg d.m. at fatigue (P less than 0.001). The total adenine nucleotide (TAN) pool (TAN = ATP + ADP + AMP) did not change after submaximal exercise but decreased significantly at fatigue (P less than 0.001). The decrease in TAN was similar to the increase in NH3. Muscle lactate was 3 +/- 1 mmol/kg d.m. at rest and increased to 104 +/- 5 mmol/kg d.m. at fatigue. Whole blood and plasma NH3 did not change significantly during submaximal but both increased significantly during maximal exercise (P less than 0.001). During maximal exercise the leg released 7,120 mumol/min of lactate, whereas only 89 mumol/min of NH3 were released. NH3 accumulation in muscle could buffer only 3% of the hydrogen ions released from lactate, and NH3 release could account for only 1% of the net hydrogen ion transport out of the cell. Muscle glutamine was constant throughout the study, whereas glutamate decreased and alanine increased during exercise (P less than 0.001). No significant changes in either arterial whole blood glutamine or glutamate were observed. Arterial plasma glutamine and glutamate concentrations, however, increased and decreased (P less than 0.001), respectively, during exercise. It is concluded that (1) muscle and blood NH3 levels increase only during strenuous exercise and (2) NH3 accumulation is of minor importance for regulating acid-base balance in body fluids during exercise.

Adult↗
PubMed1986

Leg glucose uptake during maximal dynamic exercise in humans.

Leg glucose uptake (LGU) during submaximal (50% maximal O2 uptake) and maximal dynamic exercise (97%) has been quantified from the product of the leg blood flow and the arterial minus femoral venous glucose concentration. Muscle biopsies were also obtained. During 15 min of submaximal exercise the mean LGU values ranged from 1.07 to 1.25 mmol/min, which demonstrates that LGU was stable under this condition. In contrast, during maximal exercise LGU increased continuously, reaching 2.38 +/- 0.22, 2.95 +/- 0.32, and 3.82 +/- 0.34 mmol/min after 2, 4, and 5.2 min (fatigue), respectively. The mean LGU was negatively related to the mean muscle phosphocreatine content (r = -1.00;P less than 0.01). Intracellular glucose-6-phosphate (G-6-P) and glucose were very low at rest and did not change significantly during submaximal exercise (P greater than 0.05). However, at fatigue G-6-P and glucose increased substantially and were both 8.5 mmol/kg dry muscle (P less than 0.001). These findings demonstrate that during heavy exercise glucose accumulates in the cell probably due to hexokinase inhibition by G-6-P, and thus the rate of glucose utilization appears to be lower than the rate of glucose uptake. It is suggested that 1) LGU during short-term exercise is dependent on the energy state of the muscle and 2) LGU is equal to leg glucose utilization during submaximal exercise but is in excess of utilization during heavy exercise.

Adult↗
PubMed1986

Splanchnic and peripheral glucose and lactate metabolism during and after prolonged arm exercise.

Splanchnic and peripheral exchange of glucose and gluconeogenic substrates was examined in 12 healthy subjects during 2 h of arm or leg exercise on a bicycle ergometer and during a 40-min postexercise recovery period. The work intensity corresponded to 30% of the maximal pulmonary oxygen uptake. The regional exchange of substrates was evaluated using catheter technique and indicator dilution methods for blood flow measurements. Our findings indicate that prolonged arm exercise as compared with exercise with the legs results in a greater increase in heart rate (25-40%) and a more marked reduction in splanchnic blood flow (10-30%) as well as higher arterial concentrations of lactate, free fatty acids, and catecholamines. The respiratory exchange ratio was consistently higher with arm exercise. In addition, arm exercise results in a greater fractional extraction and utilization of glucose by exercising muscle as well as a greater hepatic gluconeogenesis from lactate and glycerol. During recovery from prolonged arm exercise, leg muscle becomes an important site of lactate release to the splanchnic bed, despite a lack of net glucose uptake by the leg. Simultaneously, arm muscle shows an increase in glucose uptake in the absence of a net release of lactate. These coincident but discordant processes in the leg and arm during recovery suggest the occurrence of a redistribution of muscle glycogen from previously resting (leg) muscle to previously exercising (arm) muscle.

Adult↗