Rossi Marco, Cupisti Adamasco, Ricco Roberto, Santoro Gino, Pentimone Ferdinando, Carpi Angelo
Department of Internal Medicine, University of Pisa, Via Roma 67, 56100 Pisa, Italy.
Biomed Pharmacother. 2004 Dec;58(10):560-5. doi: 10.1016/j.biopha.2004.09.002.
We investigated the skin vasoreactivity to insulin in normal subjects and in treated non-insulin-dependent diabetes mellitus (NIDDM) patients. We measured cutaneous perfusion by laser-Doppler flowmetry (LDF) at rest and during skin cathodal iontophoresis (six pulses of 0.1 mA each for 20 s, with 40 s interval between stimulations) of insulin (0.1 ml Humulin R 100 IU/ml diluted 1/10 with of 0.9% saline solution) in 45 healthy subjects (HS), (25 males, 20 females, aged 45 +/- 18 years), and in 15 treated NIDDM patients (13 males), aged 66 +/- 8 years. Fifteen of the HS were used as controls. In these 15 sex- and age-matched HS and in the patients, we assessed also the skin postischemic hyperemia by LDF. In HS cutaneous blood flux response (CBF) to iontophoresis of insulin in saline (expressed as percent changes from baseline) was significantly higher than CBF response to iontophoresis of pure saline (maximum response: 360 +/- 51% versus 172 +/- 42%, respectively; P < 0.001, ANOVA for repeated measures). The maximum "net" CBF response to insulin (response to insulin minus response to saline) showed a negative correlation (r = -0.361; P < 0.01) with age in HS, and resulted significantly lower in the oldest than in the youngest HS (105 +/- 40% versus 307 +/- 45%, respectively; P < 0.01). No significant correlation was observed between the maximum CBF response to saline and the age of subjects. In NIDDM patients the "net" CBF response to insulin iontophoresis resulted significantly lower than in 15 sex- and age-matched control subjects (maximum response: -50 +/- 89% versus 201 +/- 81%, respectively; P < 0.001, ANOVA for repeated measures). No significant difference was observed between diabetics and controls, nor in basal perfusion (6.5 +/- 1.3 IU versus 6.8 +/- 1.7 IU, respectively) neither in the skin postischemic hyperemia (250 +/-14% versus 258 +/- 27%, respectively). These results confirm that insulin iontophoresis induces a skin vasodilatatory effect in normal subjects and show that this effect is reduced by aging and is absent in treated NIDDM patients. The local skin vasodilatatory effect induced by insulin seems to involve mechanisms different from those underlying the skin postischemic hyperemia.
我们研究了正常受试者以及接受治疗的非胰岛素依赖型糖尿病(NIDDM)患者皮肤对胰岛素的血管反应性。我们通过激光多普勒血流仪(LDF)测量了45名健康受试者(HS)(25名男性,20名女性,年龄45±18岁)和15名接受治疗的NIDDM患者(13名男性,年龄66±8岁)在静息状态下以及在皮肤阴极离子导入胰岛素(将0.1ml优泌林R 100IU/ml用0.9%盐溶液稀释1/10)期间(每次0.1mA共6个脉冲,持续20秒,刺激间隔40秒)的皮肤灌注情况。其中15名HS用作对照。在这15名性别和年龄匹配的HS以及患者中,我们还通过LDF评估了皮肤缺血后充血情况。在HS中,胰岛素盐水离子导入引起的皮肤血流反应(CBF,以相对于基线的百分比变化表示)显著高于纯盐水离子导入引起的CBF反应(最大反应分别为:360±51%对172±42%;P<0.001,重复测量方差分析)。HS中对胰岛素的最大“净”CBF反应(胰岛素反应减去盐水反应)与年龄呈负相关(r = -0.361;P<0.01),并且年龄最大的HS组显著低于年龄最小的HS组(分别为105±40%对307±45%;P<0.01)。观察到对盐水的最大CBF反应与受试者年龄之间无显著相关性。在NIDDM患者中,胰岛素离子导入引起的“净”CBF反应显著低于15名性别和年龄匹配的对照受试者(最大反应分别为:-50±89%对201±81%;P<0.001,重复测量方差分析)。糖尿病患者与对照组之间在基础灌注(分别为6.5±1.3IU对6.8±1.7IU)以及皮肤缺血后充血方面(分别为250±14%对258±27%)均未观察到显著差异。这些结果证实胰岛素离子导入在正常受试者中可诱导皮肤血管舒张效应,并表明这种效应会因衰老而降低,且在接受治疗的NIDDM患者中不存在。胰岛素诱导的局部皮肤血管舒张效应似乎涉及与皮肤缺血后充血不同的机制。