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H Vilstrup

Publications and source records attributed to H Vilstrup.

At least 109 records · Page 6Linked to original sources
PubMed1990

Effect of dietary protein on the capacity of urea synthesis in rats.

The in vivo capacity of urea nitrogen synthesis (CUNS) during alanine stimulation was measured within the blood amino acid concentration interval 7.3-11.6 mmol/l, where urea synthesis is at maximum and independent of substrate concentration. Three groups of rats were fed for 14 days, either a low protein diet (8%), a normal diet (17%), or a high protein diet (53%). Diet protein modified both CUNS and plasma glucagon concentration. CUNS was 5.86 +/- 2.93, 7.43 +/- 2.16, and 19.31 +/- 4.32 mumol/(min.100 g BW) (mean +/- SD, N = 6), respectively. The corresponding plasma glucagon concentrations after alanine stimulation were 222 +/- 400, 633 +/- 229, and 1700 +/- 627 ng/l, respectively. The in vivo kinetics of urea production is regulated by dietary protein, possibly via glucagon. This implies that the liver plays an active part in adaptation of whole body nitrogen homeostasis to dietary changes.

Alanine↗
PubMed1990

No effect of bicarbonate-induced alkalosis on urea synthesis in normal man.

The effect of metabolic alkalosis was studied in 10 healthy volunteers. In each person urea synthesis was determined in two periods of 2 h as urinary excretion corrected for accumulation in body water and for intestinal hydrolysis. Infusion of bicarbonate (115 mmol/h) increased pH of the venous blood by 0.10 units. In four subjects fasting urea synthesis was 24 mmol N/h at normal pH and unaffected by alkalosis (mean difference +/- SED was 1.04 +/- 4.1). In six subjects alanine was infused so as to increase blood alanine concentration from 0.4 to 2.5 mmol/l and urea synthesis to 107 mmol N/h. Alkalosis did not change urea synthesis (mean difference +/- SED was 1.5 +/- 7.4 mmol N/h). The results favour the view that urea synthesis mainly serves to eliminate nitrogen, but do not support the hypothesis that urea synthesis is an important immediate and direct regulatory process in acute acid-base disturbances.

Adult↗
PubMed1990

Increased hepatic efficacy of urea synthesis from alanine in insulin-dependent diabetes mellitus.

The relation of urea synthesis rate to blood alanine concentration was assessed in seven healthy controls and in 18 patients with insulin-dependent diabetes mellitus (HbAlc = 8.4 +/- 1.0% (mean +/- SD)). Following an overnight fast alanine was infused at 2 mmol h-1 kg-1 body weight. The hourly rate of urea synthesis was determined as the urinary excretion of urea corrected for accumulation of urea in total body water and intestinal hydrolysis. The functional hepatic nitrogen clearance, i.e. the relation of urea synthesis rate to blood alanine concentration, was calculated as the slope of linear regression of urea synthesis rates on blood alanine concentrations. Fasting glucagon concentrations were 85 +/- 26 ng l-1 in controls and 161 +/- 35 ng l-1 (P less than 0.01) in patients. The functional hepatic nitrogen clearances were 21.8 +/- 4.4 l h-1 in controls and 44.7 +/- 12.4 l h-1 (P less than 0.001) in patients. By multiple step-wise linear regression analysis the functional hepatic nitrogen clearance was found to correlate independently to fasting glucagon concentration, duration of diabetes, change in blood glucose and insulin following alanine infusion (r2 = 0.74). In a simple linear regression analysis the functional hepatic nitrogen clearance correlated strongly to fasting glucagon concentration (r2 = 0.54). In conclusion the kinetics of urea synthesis in insulin-dependent diabetes is changed in favour of increased conversion of alanine-N to urea-N at any blood amino acid concentration. The increased FHNC correlates strongly with hyperglucagonaemia.

Adult↗
PubMed1990

Increased amino acid clearance and urea synthesis in a patient with glucagonoma.

Fasting concentrations, clearance of exogenous infused amino acids, and lean body mass were studied in a patient with glucagonoma syndrome (fasting glucagon = 380 pmol/l, normal range 15-45 pmol). The fasting concentrations of all amino acids were reduced. The clearances of alanine, arginine, glycine, isoleucine, leucine, lysine, methionine, proline, serine, threonine, and tyrosine were increased. The urea synthesis rate during amino acid infusion was 27 mumols/kg per minute (normal range 20-24 mumols/kg per minute). The lean body mass of the patients was reduced to 59% of the expected value. It is suggested that the weight loss of patients with glucagonoma syndrome is partly due to increased hepatic conversion of amino acid nitrogen to urea nitrogen, resulting in decreased blood amino acid concentration, and secondary to this, organ protein catabolism, as shown by the decreased lean body mass.

Adenoma, Islet Cell↗
PubMed1989

Effects of xylitol versus glucose on urea synthesis and alanine metabolism in rats.

The relation between xylitol concentration (1.0 and 5.5 mmol/1), the Capacity of Urea-N Synthesis, and the rate of Alanine Metabolism was investigated in nephrectomized rats of 200 g and compared with the effect of glucose at concentrations between 5.5 and 15.5 mmol/1. The xylitol and glucose concentrations were controlled by "clamp" techniques and the endogenous hormonal effects by somatostatin. The Capacity of Urea-N Synthesis was determined during alanine infusion to constant amino acid concentrations within the interval 7.3-11.6 mmol/1. The rate of alanine metabolism was assessed as alanine infusion rate corrected for changes in alanine concentration. At normal hormonal response, xylitol at 1.0 mmol/1 and 5.5 mmol/1 reduced urea synthesis from 10.3 +/- 1.1 mumol/(min.100 g) in controls to on average 6.2 +/- 0.9 mumol/(min.100 g) (mean +/- SD, n = 2 x 10, p < 1.01). Alanine metabolism was reduced to the same extent. Glucose concentration increased from 5.4 +/- 1.0 mmol/1 in controls to 8.1 +/- 1.4 mmol/1 at both xylitol concentrations. Xylitol reduced plasma glucagon concentration to one third and tripled plasma insulin concentration. During somatostatin and blood glucose maintained above 8 mmol/1, the Capacity of Urea-N Synthesis fell to 6.1 +/- 1.0 mumol/(min.100 g). In that situation, xylitol at 1.0 mmol/1 reduced neither urea synthesis nor alanine metabolism, whereas xylitol at 5.5 mmol/1 further reduced urea synthesis to 3.4 +/- mumol/(min.100 g) (n = 10, p < 0.05) and almost stopped alanine metabolism. Thus xylitol, independently of glucose and hormonal responses, inhibited urea synthesis and alanine metabolism. This may have therapeutic implications at catabolic conditions.

Journal Article↗
PubMed1989

Nervous system damage and nutritional factors in chronic alcoholics.

Dietary habits in 45 chronic alcoholics were assessed by the dietary history method, and plasma albumin and serum transferrin. These variables as well as clinical findings did not indicate general malnutrition, but a moderate deficiency in folate intake was found. There was no correlation between the nutritional variables and central and peripheral nervous system function investigated by neuroradiological, neuropsychological, and neurophysiological methods. Transketolase and thiamine-pyrophosphate effects were measured in a subgroup of alcoholics and compared to a control group. No differences were found and there was no correlation to central nervous system impairment. These findings do not support the hypothesis that nervous system damage found in chronic alcoholics is of nutritional etiology.

Adult↗
PubMed1989

Effects of adrenalectomy on urea synthesis in rats.

The effect of depletion of glucocorticoids on the dynamics of hepatic amino-N conversion was examined 2 and 7 days after adrenalectomy in a total of 22 rats substituted by adrenaline. The capacity of urea synthesis was studied by infusion of alanine under steady state conditions with arterial concentrations of alanine between 7.3 and 11.6 mmol/l. The animals were nephrectomized and the capacity was calculated as accumulation of urea in total body water corrected for intestinal hydrolysis. Adrenalectomy reduced the capacity of urea synthesis to 55% of the capacity for control rats and reduced the alanine metabolic rate to 60%. In control rats the urea synthesis exceeded the alanine infusion by indicating an extrahepatic tissue release of amino acids. This difference disappeared after adrenalectomy. The body weight and food intake did not change during the study period. Thus lack of glucocorticoids influences the in vivo nitrogen economy both by decreasing the liver function as to conversion of amino-nitrogen and by decreasing release of tissue amino-nitrogen.

Adrenalectomy↗
PubMed1989

Vitamin B-12 and folate function in chronic alcoholic men with peripheral neuropathy and encephalopathy.

Forty-six male alcoholics hospitalized with polyneuropathy or intellectual impairment were studied after at least 2 wk of alcohol abstention. Neurological evaluation included neurophysiological examination of the sural nerve and tibial nerve, neurophysiological examinations, and CT-scanning of the brain. Alcohol and vitamin intakes were quantified by the interview method. Vitamin B-12 and folate status included examinations of peripheral blood and bone marrow aspirate, plasma vitamin B-12, plasma and erythrocyte folate, formiminoglutamic acid excretion test (FiGlu), methylmalonic acid excretion, and deoxyuridine suppression test (dU) on phytohemagglutinin-stimulated peripheral lymphocytes. The liver function was assessed by galactose elimination capacity and plasma clearance of antipyrine. There was no hematological sign of folate or vitamin B-12 deficiency. About 8% had low plasma folate, while neither erythrocyte folate nor plasma vitamin B-12 were decreased. However, half of the patients had functional folate deficiency as determined by abnormal FiGlu or dU. Compared to the remaining patients, those with abnormal FiGlu or dU had significantly more abnormal neurophysiological tests, and lower folate intake. There was no correlation between FiGlu or dU and the quantitative liver function tests. It is concluded that 1) folate deficiency may contribute to the development of alcoholic polyneuropathy, 2) the classical parameters for folate deficiency (blood concentrations, peripheral blood, and bone marrow examinations) are not reliable in diagnosing folate deficiency and 3) functional tests like FiGlu and dU are necessary to diagnose folate deficiency in alcoholics.

Adult↗
PubMed1989

Decrease in ureagenesis by partial hepatectomy does not influence acid-base balance.

It has been suggested that urea synthesis participates directly in body pH homeostasis by removal of bicarbonate. To elucidate this hypothesis sodium bicarbonate or sodium chloride was infused (11.5 mumol/min) for 90 min into control rats and into rats that had undergone an 85% hepatectomy immediately before starting the infusion. Urea synthesis rate was 2.6 +/- 0.3 mumol/min (mean +/- SE) in controls, and was significantly (P less than 0.01) reduced to 1.0 +/- 0.2 mumol/min in partially hepatectomized rats. At the start of bicarbonate infusion, pH was 7.38 and 7.34 in control and partially hepatectomized rats, respectively, and at the end of infusion, pH was 7.56 and 7.51. Standard bicarbonate at start of bicarbonate infusion was 21.9 and 21.3 mM in controls and partially hepatectomized, respectively, and it increased to 32.7 and 29.9 mM at end of infusion. In saline-infused rats a slight decrease of approximately 0.05 pH units was observed during the experiment, but again no difference emerged between control and partially hepatectomized rats. It is concluded that a major role of the liver in the regulation of acid-base balance is unlikely.

Acid-Base Equilibrium↗
PubMed1988

Exogenous hyperglucagonaemia in insulin controlled diabetic rats increases urea excretion and nitrogen loss from organs.

In order to study the effect of hyperglucagonaemia on nitrogen metabolism in diabetes, zinc protamine glucagon 60 micrograms was injected subcutaneously 3 times daily for 4 weeks into streptozotocin diabetic rats (n = 5), adequately treated with long acting insulin. This raised the plasma concentration of glucagon to 725 +/- 125 (mean +/- SEM), which is not different from that found in portal blood of uncontrolled diabetic rats: 400 +/- 75 ng/l. The controls were 5 diabetic rats treated with insulin alone and 5 non-diabetic rats. Compared with control rats the nitrogen balance was reduced (p less than 0.05) and the nitrogen contents of carcass, heart, intestines, and kidneys were reduced by 15-30% (p less than 0.05) in the glucagon treated rats. The hepatic capacity of urea synthesis and the alanine elimination rate were determined in the 3 above-mentioned groups, and confirmed in 3 identical groups followed for only 2 weeks; and in addition in a group of glucagon treated diabetic rats, where the long acting glucagon was substituted by neutral insulin the last two days before investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1988

Strict insulin therapy normalises organ nitrogen contents and the capacity of urea nitrogen synthesis in experimental diabetes in rats.

Rats with experimental diabetes due to streptozotocin (75 mg/kg body weight) and free access to food were divided into two groups. One group (n = 9) was optimally treated with insulin (glucosuria less than 4.0 mmol/24 h), using heat treated very long-acting ultralente insulin. The other group (n = 10) was poorly treated with insulin (glucosuria 20-30 mmol/24 h). The nitrogen balance and energy balance of optimally treated diabetic rats was positive and not different from the control group (n = 6). In the poorly treated diabetic rats the nitrogen balance was reduced whereas the energy balance was not different from that of control rats. After 4 weeks the fasting glucagon was: 50 +/- 21 ng/l (mean +/- SEM) in control rats, 62 +/- 18 ng/l in optimally treated diabetic rats and 249 +/- 58 ng/l in poorly treated diabetic rats (p less than 0.01). The capacity of urea nitrogen synthesis determined during alanine loading was: 9.6 +/- 1.0 mumol/(min 100 g body weight) in control rats, 10.6 +/- 1.7 mumol/(min 100 g body weight) in optimally treated diabetic rats and 17.3 +/- 1.3 mumol/(min 100 g body weight) in poorly treated diabetic rats (p less than 0.01). Nitrogen contents of carcass, heart, intestines, liver, and kidneys as determined by Kjeldahl analyses were identical in control rats and optimally treated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1988

Increased hepatic amino nitrogen conversion after elective cholecystectomy in man.

1. The effect of elective, uncomplicated cholecystectomy on plasma clearances of amino acids and on amino acid-stimulated urea synthesis was investigated in 10 patients, pre-operatively and on the first post-operative day, and compared with six controls treated identically apart from the surgery. 2. A mixture of amino acids was given as a prime-continuous infusion. Steady-state concentrations 75% higher than basal were attained and were maintained for 90 min. The clearances of amino acids were calculated as the ratios between amino acid infusion rate and the concentration. The urea synthesis rate was calculated as urinary excretion corrected for accumulation and intestinal loss. 3. After surgery the fasting plasma concentrations of alanine, arginine, glutamine plus glutamate, glycine, proline, lysine and threonine decreased by 20-30%, but were unchanged in the control group. The plasma clearance of alpha-amino nitrogen increased from 5.1 +/- 1.2 ml/s before surgery (mean +/- SD) to 6.1 +/- 1.1 ml/s (P less than 0.05, paired t-test) after surgery due to increased clearances of the above-mentioned amino acids. In the control group, the clearance decreased from 6.4 +/- 1.6 to 5.9 +/- 1.1 (P less than 0.05, paired t-test). The amino acid-stimulated urea synthesis rate after surgery was 37 +/- 9 mumol of N/s vs 30 +/- 6 (P less than 0.01, paired t-test) in the controls despite a lower alpha-amino nitrogen concentration (4.5 +/- 0.5 mmol/l vs 5.1 +/- 0.5 mmol/l, P less than 0.05, paired t-test). The post-operative urea synthesis rate exceeded the amino nitrogen infusion by 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Dexamethasone increases the capacity of urea synthesis time dependently and reduces the body weight of rats.

Rats of 230 g were treated with 0.1 mg of dexamethasone twice daily for 2 days (n = 5) and 14 days (n = 9). Controls received isotonic saline. During the first week of dexamethasone treatment the rats lost weight rapidly (up to 9 g/day). The weight loss diminished during the second week of treatment. The fasting blood insulin concentration increased sevenfold in the dexamethasone-treated rats. Fasting blood glucagon and glucose concentrations were not different from controls. In the dexamethasone-treated rats the fasting alpha-amino-N concentrations were lower: 4.0 +/- 0.3 mmol/l (mean +/- SEM) versus 6.8 +/- 0.3 mmol/l in controls. The capacity of Urea-N Synthesis, determined during alanine loading was: after 2 days of treatment 14.7 +/- 1.7 mumol/(min 100 g), after 14 days of treatment 7.9 +/- 0.8 mumol/(min 100 g), and in controls 7.5 +/- 1.0 mumol/(min 100 g) (mean +/- SEM). In conclusion, glucocorticoid treatment leads to a transient change in the liver function as to hepatic amino-N conversion, implying that more amino-N than normal is eliminated as urea-N after 2 days of treatment. This may contribute to the early, but not the late body weight loss.

Animals↗
PubMed1988

Kinetics of hepatic alanine uptake and urea synthesis in pigs.

The kinetics of hepatic alanine uptake and urea synthesis in relation to sinusoid alanine concentration was investigated in seven anesthetized pigs weighing 63 kg, using liver vein catheterizations. Each experiment consists of four steady-state periods of 40 min with alanine concentrations in the range of 0.4-27 mmol/l. The process rates were measured as the products of transhepatic concentration gradients and hepatic blood flow rate, determined by indocyanine green. The data suggest that both processes follow saturation kinetics, that there exists a sinusoidal concentration of alanine below which net removal is limited, and that urea synthesis consists of two components: one alanine independent and one depending on alanine concentration according to Michaelis-Menten kinetics. The kinetic parameters were estimated iteratively by the maximum likelihood method. The maximum rate of alanine uptake was 1.13 +/- 0.74 mmol.min-1.kg liver wt-1 (mean +/- SD), the alanine concentration resulting in half-maximum alanine uptake rate was 1.69 +/- 0.99 mmol/l, and the removal-limiting alanine concentration was 0.27 +/- 0.09 mmol/l. The maximum rate of urea-N synthesis was 1.49 +/- 0.87 mmol.min-1.kg liver wt-1, the alanine concentration resulting in half-maximum urea-N synthesis rate was 2.32 +/- 1.11 mmol/l, and the alanine concentration-independent urea-N synthesis rate was 0.13 +/- 0.10 mmol.min-1.kg liver wt-1.

Alanine↗
PubMed1988

Loss of nitrogen from organs in rats induced by exogenous glucagon.

Rats weighing 220 g were injected sc with zinc protamin glucagon 20 micrograms once daily (recurrent hyperglucagonemia) and zinc protamin glucagon 60 micrograms three times daily (chronic hyperglucagonemia); the controls received the vehicle three times daily. In the first group blood glucagon rose to above 200 ng/liter for 5 h every day; in the second group it constantly stayed above 600 ng/liter. After both 2 (n = 5) and 14 (n = 5) days treatment the control total blood alpha-amino-nitrogen (AAN) concentration was 4.3 +/- 0.1 mmol/liter, and the urea nitrogen synthesis rate was 4.9 +/- 0.4 mumol/(min.100 g BW) (mean +/- SEM) in controls. In recurrent hyperglucagonemic rats, treated for both 2 (n = 5) and 14 (n = 5) days, total AAN was 3.6 +/- 0.2 mmol/liter (P less than 0.05 vs. control) and urea nitrogen synthesis rate 4.5 +/- 0.8 mumol/(min.100 g BW). In chronic hyperglucagonemic, treated for both 2 (n = 5) and 14 (n = 5) days, total AAN was 2.2 +/- 0.1 mmol/liter (P less than 0.05 vs. control) and UNSR 7.9 +/- 0.8 mumol/(min.100g BW) (P less than 0.05 vs. control). The urea excretion was identical in controls and during recurrent hyperglucagonemia, but it was increased by 50% during chronic hyperglucagonemia. Food intake was the same in all groups. N Balances decreased from 10 mmol/24 h to 5 mmol/24 h (P less than 0.05) by chronic hyperglucagonemia. The total organ N content did not change by recurrent hyperglucagonemia, but in chronic hyperglucagonemia it decreased to 65-85% (P less than 0.01) in carcass, intestines, liver, and kidneys. In conclusion chronic but not recurrent hyperglucagonemia increases the rate of urea synthesis and decreases the blood amino acid concentration. This is suggested to be a reason for the loss of N from organs by chronic hyperglucagonemia.

Animals↗
PubMed1987

Effects of streptozotocin-induced diabetes and diet on nitrogen loss from organs and on the capacity of urea synthesis in rats.

Rats with experimental streptozotocin-induced diabetes (75 mg/kg) were divided into two groups. One group was free fed (n = 8), the other group (n = 7) pair fed to a group of control animals (n = 8). The nitrogen and energy balances of the control rats were positive. In the free-fed diabetic rats the nitrogen balance was neutral and the energy balance higher than in controls. In the pair-fed diabetic rats the nitrogen balance was negative and the energy balance reduced. After 4 weeks the capacity of urea-nitrogen synthesis was: 8.1 +/- 0.6 mumol/(min 100 g body weight) (mean +/- SEM) in controls and 22.2 +/- 2.2 mumol/(min 100 g body weight) in both groups of diabetic rats. Initially, the whole body nitrogen content was 453 +/- 9 mmol. Four weeks later it was 536 +/- 19 mmol in controls, 410 +/- 21 mmol in the free-fed diabetic rats, and 315 +/- 6 mmol in the pair-fed diabetic rats. The largest changes occurred in the muscles, initially containing 278 +/- 6 mmol, 4 weeks later 328 +/- 8 mmol, compared to 234 +/- 19 in the free-fed diabetic rats and 166 +/- 18 mmol in the pair-fed diabetic rats. In conclusion uncontrolled diabetes is characterised by loss of nitrogen from muscles and most other organs. The losses from some organs are preventable by increased food intake. Irrespective of food intake the hepatic dynamics of amino nitrogen conversion is changed in a way that favours protein catabolism.

Animals↗