Schmitt F, Bresson J L, Beressi N, Bichet D G, Chauveau D, Bankir L
INSERM Unité 367, Institut du Fer à Moulin, Paris.
Diabetes Metab. 2003 Sep;29(4 Pt 1):352-61. doi: 10.1016/s1262-3636(07)70046-0.
Vasopressin (VP) is known to be elevated in patients with diabetes mellitus (DM). While the influence of acute hyperglycemia has been ruled out, the mechanism or the osmotically active compound responsible for the increase in VP secretion is still not elucidated. Because the plasma level of several amino acids (AAs) is increased in DM, we evaluated whether AAs could represent an effective osmotic stimulus for VP secretion.
In a cross-over study, eight healthy volunteers randomly received an infusion of isotonic saline (control) or mixed AA solution, i.v., at a low or a high rate (2 or 4.5 mg/min/kg BW, respectively). Plasma VP (P(VP)) was measured for two hours before and three hours during AA or control infusion.
AA infusion induced a dose-dependent elevation in plasma AA concentration but did not alter P(VP). However, effective plasma osmolality (P(osm)) (osmolality minus urea concentration) remained unchanged because a concommittant fall in plasma sodium concentration (P(Na)), likely due to sodium-linked uptake of AA in peripheral cells, compensated for the rise in plasma AA.
The stability of effective P(osm) may explain the lack of change observed in P(VP). Because sodium is a very efficient stimulus for VP secretion, it may be assumed that the fall in P(Na) occurring during AA infusion should have reduced VP secretion and thus P(VP). In this setting, the stability of P(VP) suggests that AAs induced an increase in VP secretion which counterbalanced the fall attributable to the decrease in P(Na). In conclusion, in acute experiments, AAs seem to represent an effective stimulus for VP secretion, almost equally potent as sodium. Further studies are needed to evaluate their contribution to the high P(VP) seen in the chronic setting of DM.
已知糖尿病（DM）患者体内血管加压素（VP）水平升高。虽然急性高血糖的影响已被排除，但导致VP分泌增加的机制或渗透活性化合物仍未阐明。由于DM患者体内几种氨基酸（AA）的血浆水平升高，我们评估了AA是否可能是VP分泌的有效渗透刺激物。
在一项交叉研究中，8名健康志愿者随机接受静脉输注等渗盐水（对照）或低速率或高速率（分别为2或4.5mg/min/kg体重）的混合AA溶液。在输注AA或对照前2小时和输注期间3小时测量血浆VP（P(VP)）。
输注AA导致血浆AA浓度呈剂量依赖性升高，但未改变P(VP)。然而，有效血浆渗透压（P(osm)）（渗透压减去尿素浓度）保持不变，因为血浆钠浓度（P(Na)）同时下降，这可能是由于外周细胞中与钠相关的AA摄取，抵消了血浆AA的升高。
有效P(osm)的稳定性可能解释了P(VP)未观察到变化的原因。由于钠是VP分泌的非常有效的刺激物，可以假设在输注AA期间发生的P(Na)下降应该会减少VP分泌，从而降低P(VP)。在这种情况下，P(VP)的稳定性表明AA诱导了VP分泌增加，抵消了由于P(Na)降低而导致的下降。总之，在急性实验中，AA似乎是VP分泌的有效刺激物，几乎与钠一样有效。需要进一步研究来评估它们在DM慢性情况下高P(VP)中的作用。
