Urea synthesis in patients with chronic pancreatitis: relation to glucagon secretion and dietary protein intake.
OBJECTIVE
Up-regulation of urea synthesis by amino acids and dietary protein intake may be impaired in patients with chronic pancreatitis (CP) due to the reduced glucagon secretion. Conversely, urea synthesis may be increased as a result of the chronic inflammation. The aims of the study were to determine urea synthesis kinetics in CP patients in relation to glucagon secretion (study I) and during an increase in protein intake (study II).


METHODS
In study I, urea synthesis rate, calculated as urinary excretion rate corrected for accumulation in total body water and intestinal loss, was measured during infusion of alanine in 7 CP patients and 5 control subjects on spontaneous protein intake. The functional hepatic nitrogen clearance (FHNC), i.e. urea synthesis expressed independent of changes in plasma amino acid concentration, was calculated as the slope of the linear relation between urea synthesis rate and plasma alpha -amino nitrogen concentration. In study II, 6 of the patients of study I had urea synthesis and FHNC determined before and after a period of 14 days of supplementation with a protein-enriched liquid (dietary sequence randomized).


RESULTS
Study I: Alanine infusion increased urea synthesis rate by a factor of 10 in the control subjects, and by a factor of 5 in the CP patients (P<0.01). FHNC was 31.9+/-2.4 l/h in the control subjects and 16.5+/-2.0 l/h (P<0.05) in the CP patients. The glucagon response to alanine infusion (AUC) was reduced by 75 % in the CP patients. The reduction in FHNC paralleled the reduced glucagon response (r(2)=0.55, P<0.01). Study II: The spontaneous protein intake was 0.75+/-0.14 g/(kg x day) and increased during the high protein period to 1.77+/-0.12 g/(kg x day). This increased alanine stimulated urea synthesis by a factor of 1.3 (P<0.05), FHNC from 13.5+/-2.6 l/h to 19.4+/-3.1 l/h (P<0.01), and the glucagon response to alanine infusion (AUC) by a factor of 1.8 (P<0.05).


CONCLUSIONS
Urea synthesis rate and FHNC are markedly reduced in CP patients. This is associated with, and probably a result of, impaired glucagon secretion, and predicts a lower than normal postprandial hepatic loss of amino nitrogen. An increase in dietary protein intake increases alanine stimulated urea synthesis and FHNC by a mechanism that involves an increase in glucagon. This indicates that the low FHNC during spontaneous protein intake included an adaptation to the low protein intake, effectuated by a further decrease in glucagon secretion.
Hamberg
O
O
Department of Medicine M, Glostrup University Hospital, Copenhagen, Denmark.
Andersen
V
V
Sonne
J
J
Larsen
S
S
Vilstrup
H
H
D000222:Adaptation, Physiological; D000328:Adult; D000409:Alanine / Q000008:administration & dosage / Q000493:pharmacokinetics; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002908:Chronic Disease; D004044:Dietary Proteins / Q000008:administration & dosage*; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009584:Nitrogen / Q000378:metabolism; D010195:Pancreatitis / Q000378:metabolism*; D014508:Urea / Q000378:metabolism*
D001786:Blood Glucose; D002096:C-Peptide; D004044:Dietary Proteins; D007328:Insulin; D014508:Urea; D005934:Glucagon; D009584:Nitrogen; D000409:Alanine