Hamberg O, Andersen V, Sonne J, Larsen S, Vilstrup H
Department of Medicine M, Glostrup University Hospital, Copenhagen, Denmark.
Clin Nutr. 2001 Dec;20(6):493-501. doi: 10.1054/clnu.2001.0476.
BACKGROUND & AIMS: 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).
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).
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).
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.
由于胰高血糖素分泌减少，慢性胰腺炎（CP）患者中氨基酸和膳食蛋白质摄入引起的尿素合成上调可能受损。相反，慢性炎症可能导致尿素合成增加。本研究的目的是确定CP患者中与胰高血糖素分泌相关的尿素合成动力学（研究I）以及蛋白质摄入量增加时的尿素合成动力学（研究II）。
在研究I中，对7例CP患者和5例自发摄入蛋白质的对照受试者输注丙氨酸期间，测量尿素合成速率（以校正全身水蓄积和肠道损失后的尿排泄率计算）。功能性肝氮清除率（FHNC），即独立于血浆氨基酸浓度变化表示的尿素合成，计算为尿素合成速率与血浆α-氨基氮浓度之间线性关系的斜率。在研究II中，研究I中的6例患者在补充富含蛋白质的液体14天前后（饮食顺序随机）测定尿素合成和FHNC。
研究I：输注丙氨酸使对照受试者的尿素合成速率增加了10倍，使CP患者的尿素合成速率增加了5倍（P<0.01）。对照受试者的FHNC为31.9±2.4 l/h，CP患者为16.5±2.0 l/h（P<0.05）。CP患者对丙氨酸输注的胰高血糖素反应（AUC）降低了75%。FHNC的降低与胰高血糖素反应的降低平行（r²=0.55，P<0.01）。研究II：自发蛋白质摄入量为0.75±0.14 g/（kg·天），在高蛋白期增加至1.77±0.12 g/（kg·天）。这种增加的丙氨酸刺激使尿素合成增加了1.3倍（P<0.05），FHNC从13.5±2.6 l/h增加至19.4±3.1 l/h（P<0.01），对丙氨酸输注的胰高血糖素反应（AUC）增加了1.8倍（P<0.05）。
CP患者的尿素合成速率和FHNC明显降低。这与胰高血糖素分泌受损相关，可能是其结果，并预示餐后肝脏氨基氮损失低于正常水平。膳食蛋白质摄入量增加通过涉及胰高血糖素增加的机制增加丙氨酸刺激的尿素合成和FHNC。这表明自发蛋白质摄入期间低FHNC包括对低蛋白质摄入的适应，这是由胰高血糖素分泌的进一步降低实现的。
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