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Biomedical subjects

J Wahren

Publications and source records attributed to J Wahren.

At least 73 records · Page 4Linked to original sources
PubMed1995

Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients.

To elucidate the mechanism of insulin's anticatabolic effect in humans, protein dynamics were evaluated in the whole-body, splanchnic, and leg tissues in six C-peptide-negative type I diabetic male patients in the insulin-deprived and insulin-treated states using two separate amino acid models (leucine and phenylalanine). L-(1-13C,15N)leucine, L-(ring-2H5)phenylalanine, and L-(ring-2H2) tyrosine were infused intravenously, and isotopic enrichments of [1-13C,15N]-leucine, (13C)leucine, (13C)ketoisocaproate, (2H5)phenylalanine, [2H4]tyrosine, (2H2)tyrosine, and 13CO2 were measured in arterial, hepatic vein, and femoral vein samples. Whole-body leucine flux, phenylalanine flux, and tyrosine flux were decreased (< 0.01) by insulin treatment, indicating an inhibition of protein breakdown. Moreover, insulin decreased (< 0.05) the rates of leucine oxidation and leucine transamination (P < 0.01), but the percent rate of ketoisocaproate oxidation was increased by insulin (P < 0.01). Insulin also reduced (< 0.01) whole-body protein synthesis estimated from both the leucine model (nonoxidative leucine disposal) and the phenylalanine model (disposal of phenylalanine not accounted by its conversion to tyrosine). Regional studies demonstrated that changes in whole body protein breakdown are accounted for by changes in both splanchnic and leg tissues. The changes in whole-body protein synthesis were not associated with changes in skeletal muscle (leg) protein synthesis but could be accounted for by the splanchnic region. We conclude that though insulin decreases whole-body protein breakdown in patients with type I diabetes by inhibition of protein breakdown in splanchnic and leg tissues, it selectively decreases protein synthesis in splanchnic tissues, which accounted for the observed decrease in whole-body protein synthesis. Insulin also augmented anabolism by decreasing leucine transamination.

Adult↗
PubMed1994

Does C-peptide have a physiological role?

Short-term administration of physiological amounts of C-peptide to patients with insulin-dependent diabetes was found to reduce the glomerular hyperfiltration in these patients as well as augment whole body glucose utilization. It could also be shown that C-peptide administration increases blood flow, oxygen uptake and capillary diffusion capacity of exercising forearm muscle in IDDM patients, probably by increasing capillary recruitment in the working muscle. Studies under in vitro conditions have shown that C-peptide stimulates glucose transport in skeletal muscle with its maximal effect within the physiological concentration range. The findings in a clinical study in which IDDM patients were given C-peptide and insulin or insulin alone for 4 weeks in a double-blind randomized study design, indicate that C-peptide improves renal function by reducing urinary albumin excretion and glomerular filtration, decreases blood retinal barrier leakage and improves metabolic control. Preliminary findings suggest that C-peptide administration on a short-term basis (3h) may ameliorate autonomic neuropathy by restoring to near normal the heart rate variability in response to expiration and inspiration. Insight into a possible mechanism of action of C-peptide is provided by the finding that C-peptide stimulates Na+K(+)-ATPase activity in renal tubular segments. In conclusion, the present results suggest that, contrary to the prevailing view, C-peptide possesses important physiological effects.

Animals↗
PubMed1994

Glucose absorption and production following oral glucose: comparison of compartmental and arteriovenous-difference methods.

Both whole-body models and the regional arteriovenous (AV)-difference method have been used to calculate systemic glucose rates of appearance (Ras) under non-steady-state conditions. Although whole-body models have been experimentally validated in the dog, direct comparison of the whole-body and regional-balance approach has not been made in man. We reanalyzed published data obtained by combining the double-tracer technique ([3H]glucose infusion with ingestion of a [14C]glucose-labeled load) with hepatic vein catheterization. Steele's monocompartmental model underestimated the Ra of oral glucose ([RaO] by 12%, P < .0001) and overestimated the Ra of endogenous glucose ([RaE] by 19%, P < .0001) in comparison to a two-compartment (2-c) model calculation. Splanchnic balance data were used to compute the total glucose Ra (RaT) with either steady-state or non-steady-state equations (the latter by estimating splanchnic transit times). Except for one early time point (15 minutes), the two calculations agreed well with one another. The glucose RaT by the balance method was well correlated with that calculated by the 2-c whole-body model (r = .72, P < .0001 on all data points); however, the former significantly underestimated the latter by 0.62 mg.min-1.kg-1 (or 13%, P < .01) on average throughout the absorptive period. This bias was small in comparison to the estimated random error affecting the calculation of glucose RaT by the model, which averaged 1.4 mg.min-1.kg-1 (corresponding to a variation coefficient of approximately 30%).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Influence of protein ingestion on human splanchnic and whole-body oxygen consumption, blood flow, and blood temperature.

Splanchnic and whole-body oxygen uptake, blood flow, and blood temperature were studied in 10 healthy subjects before and during 2 hours after oral ingestion of 900 kJ of fish protein. Indirect calorimetry and catheter techniques were used, including blood thermometry in arterial, pulmonary arterial, and hepatic venous blood. After the meal, pulmonary oxygen uptake increased from a basal value of 272 +/- 11 to 332 +/- 23 mL/min. During the first postprandial hour, splanchnic oxygen uptake increased from 62 +/- 5 to 93 +/- 9 mL/min (+50%, P < .05), thereby accounting for 62% +/- 17% of the simultaneous increase in whole-body oxygen consumption. During the second postprandial hour, splanchnic oxygen uptake increased no further, whereas in the extrasplanchnic tissues the oxygen consumption increased, now accounting for the entire simultaneous increase in pulmonary oxygen uptake. Cardiac output increased from basal 6.4 +/- 0.4 to 7.5 +/- 0.5 L/min. Splanchnic blood flow changed little while the arteriohepatic venous oxygen difference increased from 46 +/- 3 to 54 +/- 4 mL/L. Arterial and hepatic venous blood temperatures increased by almost 0.3 degrees C, reflecting a considerable accumulation of heat, indicating a conversion into a positive thermal balance. It is concluded that after protein ingestion, (1) oxygen uptake increases mainly in the splanchnic organs during the first hour, and thereafter exclusively in the extrasplanchnic tissues; (2) the blood flow increases mainly in extrasplanchnic tissues; and (3) the blood temperature increases almost linearly, indicating an upward adjustment of the temperature setpoint in the central thermosensors.

Adult↗
PubMed1994

Splanchnic and peripheral glucose metabolism in cirrhosis.

The effects of glucose and insulin administration on splanchnic and leg exchange of glucose were investigated in seven patients with cirrhosis and six sex- and age-matched healthy controls using the catheter technique. After a basal period, glucose infusion (1 mg.kg-1.min-1) was given for 45 min, followed by a 2-h euglycemic insulin clamp (1 mU.kg-1.min-1). In the basal state insulin levels were significantly higher in patients than in controls (25 +/- 4 vs. 7 +/- 2 microU/ml). Net splanchnic glucose output tended to be lower in patients than in controls (0.50 +/- 0.16 vs 0.73 +/- 0.11 mmol/min nonsignificant), as did leg glucose uptake (0.06 +/- 0.01 vs 0.08 +/- 0.02 mmol/min, non-significant). Glucose infusion resulted in a significant rise in leg glucose uptake, while net splanchnic glucose output decreased in both groups. During the euglycemic insulin clamp, insulin concentrations rose to 110 +/- 10 and 80 +/- 8 microU/ml in patients and controls, respectively. C-peptide concentrations decreased in the healthy controls but were unchanged from the basal level in patients with cirrhosis. Glucose disposal during the last half hour of the clamp was 1.12 +/- 0.08 and 3.19 +/- 0.04 mmol/min in patients and controls, respectively (p < 0.001). Glucose was taken up by the splanchnic region in both groups but this uptake was significantly greater in patients than in controls (0.42 +/- 0.05 vs. 0.25 +/- 0.06 mmol/min, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Augmented thermic effect of amino acids under general anaesthesia: a mechanism useful for prevention of anaesthesia-induced hypothermia.

1. Intravenous infusion of amino acids stimulates energy expenditure and heat accumulation in normal man. To find out whether such stimulation also occurs during general anaesthesia, thermogenesis was measured in 21 patients before, during and after anaesthesia and surgery. 2. Ten patients received a mixture of 19 amino acids (240 kJ/h) infused intravenously throughout the anaesthesia. The other 11 patients, serving as controls, received saline. Using catheters previously inserted into the pulmonary and a systemic artery, cardiac output, arteriovenous oxygen difference, pulmonary oxygen uptake and mixed blood temperature were measured. 3. During anaesthesia and surgery, the blood temperature fell by 0.67 +/- 0.09 degrees C/h in the control patients and by 0.38 +/- 0.06 degrees C/h in the amino acid-treated patients. Anaesthesia during 34 +/- 4 min before surgery reduced the pulmonary oxygen uptake by 145 +/- 9 ml/min in the control patients and by 81 +/- 10 ml/min in the amino acid-treated patients, corresponding to reductions in total energy expenditure of 47 W in the control group and 26 W in the amino acid-treated group. The difference, 21 W, illustrates the thermogenic action of the amino acids. This value may be compared with that of 4 W, observed in unanaesthetized individuals subjected to 30 min of identical amino acid infusions. 4. At awakening after the anaesthesia, the oxygen consumption rose to 71 +/- 21% above the pre-anaesthesia level in the amino acid-treated patients, who, without shivering, rapidly returned to normothermia, whereas in the control patients the oxygen uptake remained slightly below the pre-anaesthesia level, despite sustained hypothermia and vigorous shivering.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Glucose-induced thermogenesis in tetraplegic patients with low sympathoadrenal activity.

The influence of the sympathoadrenal system on the thermic effect of glucose was examined by studying six tetraplegic patients with complete lesions of the cervical spinal cord. Indirect calorimetry and catheter techniques were employed, and measurements were made before and during 2 h after oral ingestion of 75 g of glucose. The results were compared with previous findings from an identical study in healthy subjects and with those from a control group of five tetraplegic patients receiving water instead of glucose. In response to glucose, energy expenditure rose from 69 +/- 5 to 79 +/- 5 and from 88 +/- 3 to 98 +/- 4 W, (not significant) in the patients and healthy subjects, respectively. In both patients and the healthy subjects the postprandial oxygen consumption increased exclusively in extrasplanchnic tissues. Splanchnic blood flow, which in normals increased 34 +/- 1%, did not change in the patients after glucose. Blood temperatures were unchanged in normals after glucose but rose by approximately 0.5 degrees C in the patients. The patients' arterial plasma concentrations of norepinephrine were low in the basal state and did not rise significantly after glucose. The arterial blood glucose concentrations after glucose were significantly higher in the patients than in the healthy subjects. Insulin levels rose to 105 +/- 20 mU/l in the patients and to 59 +/- 7 mU/l in the controls (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1994

Effects of i.v. amino acids on human splanchnic and whole body oxygen consumption, blood flow, and blood temperatures.

The thermic effect of amino acid administration was examined in healthy subjects. Pulmonary and splanchnic oxygen uptake, cardiac output, splanchnic blood flow, and blood temperatures were measured in eight healthy men before and during 2.5 h of intravenous infusion of 600 kJ of a mixture of 19 amino acids. Indirect calorimetry and catheter techniques were used, including thermometry in arterial and a hepatic venous blood. During the infusion, pulmonary oxygen uptake rose progressively from a basal value of 269 +/- 6 to 321 +/- 8 ml/min after 2.5 h. The splanchnic oxygen consumption increased from a basal level of 64 +/- 4 to a peak value of 91 +/- 7 ml/min after 2 h of infusion. The 2.5 h average splanchnic proportion of the amino acid-induced whole body thermogenesis was 51 +/- 11%. Cardiac output increased from 6.2 +/- 0.3 in the basal state to 7.3 +/- 0.4 l/min, whereas the splanchnic blood flow remained unchanged during the infusion period. The arteriohepatic venous oxygen difference increased from 51 +/- 4 in the basal state to 65 +/- 5 ml/l after 2 h of amino acid infusion. The blood temperature rose by approximately 0.25 degrees C during the amino acid infusion, reflecting an increased heat accumulation in the body. It is concluded that the splanchnic tissues account for approximately one-half of the amino acid-induced whole body thermogenesis, that amino acid infusion augments blood flow in the extrasplanchnic but not in the splanchnic tissues, and stimulates the accumulation of heat in the body most likely via a resetting of the central thermosensors.

Adult↗
PubMed1994

Renal oxygen consumption, thermogenesis, and amino acid utilization during i.v. infusion of amino acids in man.

The renal contribution to the amino acid-induced whole body thermogenesis was examined. Using indirect calorimetry and catheter techniques, pulmonary and renal oxygen uptake and blood flow, blood temperatures, and net renal exchange of amino acids, glucose and lactate were measured in eight healthy men before and during 3 h of intravenous infusion of 720 kJ of an amino acid solution. During the infusion, the pulmonary oxygen uptake increased from 252 +/- 12 to 310 +/- 8 ml/min, cardiac output increased from 5.9 +/- 0.3 to 6.8 +/- 0.3 l/min, and the arterial blood temperature increased from 36.34 +/- 0.04 to 36.68 +/- 0.07 degrees C. Renal oxygen consumption, heat production, blood flow, and net glucose exchange remained unchanged during the infusion. The net renal uptake of amino acid energy from the blood rose from 2 +/- 2 to 11 +/- 4 W. The total renal energy expenditure was 9-10 W throughout the study period. It is concluded that intravenous amino acid infusion greatly augments the uptake and utilization of amino acids in the kidneys but does not stimulate the renal oxygen consumption, heat production, blood flow, or glucose release.

Adult↗
PubMed1994

Effect of insulin on the hepatic production of insulin-like growth factor-binding protein-1 (IGFBP-1), IGFBP-3, and IGF-I in insulin-dependent diabetes.

Insulin-like growth factors (IGFs) circulate attached to binding proteins (IGFBPs). Only the unbound form of IGF is suggested to be biological active. The main source of circulating IGF-I and IGFBP-1 is considered to be the liver, but that of circulating IGFBP-3 is not known. IGF-I and IGFBP-3 are GH dependent, whereas IGFBP-1 is insulin regulated. The aim of the present study was to examine the effect of insulin on the hepatic secretion of IGFBP-1, IGFBP-3, and IGF-I. Seven insulin-dependent diabetic patients in whom insulin was withheld for 12 h were studied in the overnight fasted state. Blood was sampled simultaneously from the hepatic vein, a peripheral vein, and an artery before and during insulin infusion for 3 h. The basal IGFBP-1 levels in the peripheral vein were several-fold elevated (249 +/- 44 micrograms/L) compared to those in healthy subjects (37 +/- 2 micrograms/L). Fasting IGFBP-1 concentrations were inversely correlated to the insulin levels (r = -0.918; P < 0.001). The mean IGF-I concentration (175 +/- 17 micrograms/L; -1.62 +/- 0.38 SD score) was decreased compared with that in age-matched healthy subjects. The basal IGFBP-3 levels in the peripheral vein (4.50 +/- 0.33 mg/L) were within the normal range. There was a significant correlation in the hepatic vein between fasting IGF-I and IGFBP-3 levels (r = 0.928; P < 0.001). Basal splanchnic IGFBP-1 production was 18 +/- 7 micrograms/min, whereas no basal net exchanges of IGF-I or IGFBP-3 were observed across the splanchnic area. Insulin inhibited splanchnic IGFBP-1 production within 120 min and glucose output within 20 min. Serum IGF-I, but not IGFBP-3, concentrations increased significantly during the insulin infusion. In summary, this study demonstrates the existence of considerable IGFBP-1 production from the liver during insulinopenia and the complete blocking of splanchnic IGFBP-1 production and increases in serum levels of IGF-I by insulin despite no effect on IGFBP-3 levels. Thus, insulin may play a role in determining the bioavailability of IGF-I.

Adult↗
PubMed1993

Quantitation of the pathways followed in the conversion of fructose to glucose in liver.

Recently, only about 50% of the conversion of fructose to glucose was reported to be via fructose-1-P aldolase catalysis in children. This was also suggested to be the case in adults. That possibility has been tested using a method that quantifies the pathways of fructose conversion to glucose via the fate of 14C from specifically labeled fructose. Trace [6-14C] fructose or its immediate precursor [6-14C]sorbitol with unlabeled fructose (0.3 mg/kg body weight/min) was given intravenously or intragastrically with trace [1-14C]lactate to six normal adults fasted overnight. The distributions of 14C in glucose from blood samples were determined. The ratios of 14C in C1 to C6 of the glucose were equal to or only slightly less than the ratios of 14C in C3 to C4. Since incorporation into C3 and C4 of glucose must have arisen via the conversion of [1-14C]lactate to [1-14C]triose phosphates, fructose conversion to glucose must also have arisen predominantly via the triose phosphates. From the ratios, 85.1% to 100%, a mean of 94.9% of the fructose converted to glucose is calculated to have been converted to glucose with cleavage of the carbon skeleton of the fructose. These findings contrast with the report that in children under similar conditions only about 50% of the conversion of fructose to glucose is with cleavage. The findings agree with previous results in which fructose was administered to normal adults as a bolus at a dose of 60 mg/kg body weight. The possible reasons that the findings in children are different from those in adults are considered.

Adult↗
PubMed1993

Meal-induced rise in resting energy expenditure in patients with complete cervical spinal cord lesions.

Central activation of the sympathoadrenal system is generally considered to be an essential component of the mechanisms whereby food ingestion stimulates resting energy expenditure. The functional importance of such sympathoadrenal stimulation has been demonstrated primarily in animals. To the extent that central sympathoadrenal stimulation is required for normal human nutrient-induced thermogenesis, this process should be defective in patients with complete cervical spinal cord lesion and severed connection between the central nervous system and the peripheral sympathetic nerves. Consequently, respiratory gas exchange was measured by indirect calorimetry in 9 tetraplegic patients and in 6 healthy individuals. Measurements were performed before and 2 hours after ingestion of a standardised mixed meal (40% of basal 24 h energy requirements). The basal energy expenditure was 64 +/- 4 watts in the tetraplegic patients and 79 +/- 6 watts in the controls. After the meal, energy expenditure increased on average by 17 +/- 2 watts or 26 +/- 3% of the basal values in the patients and by 14 +/- 2 watts or 19 +/- 3% in the healthy controls (NS). The thermic effect of the meal, ie the rise in energy expenditure expressed in percent of the meal's energy content, was 5.5 +/- 0.7% in the patients and 3.8 +/- 0.6% in the controls (NS). Plasma concentrations of noradrenaline were low in the tetraplegic patients (0.3-0.4 nmol/l) compared to the healthy controls (1.1-1.4 nmol/l), p < 0.02. It is concluded that nutrient-induced thermogenesis in tetraplegic patients with low sympathoadrenal activity is not diminished compared to healthy controls. The findings indicate that efferent sympathoadrenal stimulation from the brain is not a causal necessity for nutrient-induced thermogenesis in man.

Adult↗
PubMed1993

Whole body and splanchnic oxygen consumption and blood flow after oral ingestion of fructose or glucose.

The contribution of the splanchnic tissues to the initial 2-h rise in whole body energy expenditure after ingestion of glucose or fructose was examined in healthy subjects. Indirect calorimetry and catheter techniques were employed to determine pulmonary gas exchange, cardiac output, splanchnic blood flow, splanchnic oxygen uptake, and blood temperatures before and for 2 h after ingestion of 75 g of either fructose or glucose in water solution or of water only. Fructose ingestion was found to increase total oxygen uptake by an average of 9.5% above basal levels; the corresponding increase for glucose was 8.8% and for water only 2.5%. The respiratory exchange ratio increased from 0.84 in the basal state to 0.97 at 45 min after fructose ingestion and rose gradually after glucose to 0.86 after 120 min. The average 2-h thermic effect, expressed as percent of ingested energy, was 5.0% for fructose and 3.7% for glucose (not significant). Splanchnic oxygen consumption did not increase measurably after ingestion of either fructose or glucose. The arterial concentration of lactate rose, arterial pH fell, and PCO2 remained essentially unchanged after fructose ingestion. Glucose, but not fructose, elicited increases in cardiac output (28%) and splanchnic blood flow (56%). Fructose, but not glucose, increased arterial blood temperature significantly. It is concluded that both fructose and glucose-induced thermogenesis occurs exclusively in extrasplanchnic tissues. Compared with glucose, fructose ingestion is accompanied by a more marked rise in CO2 production, possibly reflecting an increased extrasplanchnic oxidation of lactate and an accumulation of heat in the body.

Adult↗
PubMed1993

14C-labeled propionate metabolism in vivo and estimates of hepatic gluconeogenesis relative to Krebs cycle flux.

Purposes of this study were 1) to estimate in humans, using 14C-labeled propionate, the rate of hepatic gluconeogenesis relative to the rate of Krebs cycle flux; 2) to compare those rates with estimates previously made using [3-14C]lactate and [2-14C]acetate; 3) to determine if the amount of ATP required for that rate of gluconeogenesis could be generated in liver, calculated from that rate of Krebs cycle flux and splanchnic balance measurements, previously made, and 4) to test whether hepatic succinyl-CoA is channeled during its metabolism through the Krebs cycle. [2-14C]propionate, [3-14C]-propionate, and [2,3-14C]succinate were given along with phenyl acetate to normal subjects, fasted 60 h. Distributions of 14C were determined in the carbons of blood glucose and of glutamate from excreted phenylacetylglutamine. Corrections to the distributions for 14CO2 fixation were made from the specific activities of urinary urea and the specific activities in glucose, glutamate, and urea previously found on administering [14C]-bicarbonate. Uncertainties in the corrections and in the contributions of pyruvate and Cori cyclings limit the quantitations. The rate of gluconeogenesis appears to be two or more times the rate of Krebs cycle flux and pyruvate's decarboxylation to acetyl-CoA, metabolized in the cycle, less than one-twenty-fifth the rate of its decarboxylation. Such estimates were previously made using [3-14C]lactate. The findings support the use of phenyl acetate to sample hepatic alpha-ketoglutarate. Ratios of specific activities of glucose to glutamate and glucose to urinary urea and expired CO2 indicate succinate's extensive metabolism when presented in trace amounts to liver. Utilizations of the labeled compounds by liver relative to other tissues were in the order succinate = lactate > propionate > acetate. ATP required for gluconeogenesis and urea formation was approximately 40% of the amount of ATP generated in liver. There was no channeling of succinyl-CoA in the Krebs cycle in the hepatic mitochondria.

Adult↗
PubMed1993

Influence of combined C-peptide and insulin administration on renal function and metabolic control in diabetes type 1.

The possible influence of C-peptide on renal function and metabolic control in patients with type 1 diabetes was examined in a double blind, randomized study. Nine patients received insulin and equimolar amounts of biosynthetic human C-peptide for 1 month (group 1), and nine were given insulin only (group 2). C-Peptide levels in plasma ranged from 0.3-2.6 nmol/L in group 1 during the study, whereas group 2 had undetectable levels. The urinary excretion of albumin in group 1 was 21 +/- 6 micrograms/min before the study and decreased by 40% and 55% after 2 and 4 weeks, respectively (P < 0.05). No change was seen in group 2. The glomerular filtration rate fell by 6% after 2 and 4 weeks (P < 0.05) in group 1, whereas no change was observed in group 2. Fluorescein leakage across the blood-retinal barrier decreased by 30% in group 1 (P < 0.05) and was unaltered in group 2. Hemoglobin-A1c and fructosamine values decreased by 9-16% in group 1 (P < 0.05), but not in group 2. The findings suggest that administration of C-peptide plus insulin, compared to insulin alone, to type 1 diabetic patients may reduce glomerular permeability and improve metabolic control.

Adolescent↗