Lugari R, Dell'Anna C, Ugolotti D, Dei Cas A, Barilli A L, Zandomeneghi R, Marani B, Iotti M, Orlandini A, Gnudi A
Department of Endocrinology, University of Parma, Italy.
Horm Metab Res. 2000 Oct;32(10):424-8. doi: 10.1055/s-2007-978665.
Exogenous glucagon-like peptide 1(GLP-1) bioactivity is preserved in type 2 diabetic patients, resulting the peptide administration in a near-normalization of plasma glucose mainly through its insulinotropic effect. GLP-1 also reduces meal-related insulin requirement in type 1 diabetic patients, suggesting an impairment of the entero-insular axis in both diabetic conditions. To investigate this metabolic dysfunction, we evaluated endogenous GLP-1 concentrations, both at fasting and in response to nutrient ingestion, in 16 type 1 diabetic patients (age = 40.5 +/- 14yr, HbA1C = 7.8 +/- 1.5%), 14 type 2 diabetics (age = 56.5 +/- 13yr, HbA1C = 8.1 +/- 1.8%), and 10 matched controls. In postabsorptive state, a mixed breakfast (230 KCal) was administered to all subjects and blood samples were collected for plasma glucose, insulin, C-peptide and GLP-1 determination during the following 3 hours. In normal subjects, the test meal induced a significant increase of GLP-1 (30', 60': p < 0.01), returning the peptide values towards basal concentrations. In type 2 diabetic patients, fasting plasma GLP-1 was similar to controls (102.1 +/- 1.9 vs. 97.3 +/- 4.01 pg/ml), but nutrient ingestion failed to increase plasma peptide levels, which even decreased during the test (p < 0.01). Similarly, no increase in postprandial GLP-1 occurred in type 1 diabetics, in spite of maintained basal peptide secretion (106.5 +/- 1.5 pg/ml). With respect to controls, the test meal induced in both diabetic groups a significant increase in plasma glucagon levels at 60' (p < 0.01). In conclusion, either in condition of insulin resistance or insulin deficiency chronic hyperglycemia, which is a common feature of both metabolic disorders, could induce a progressive desensitization of intestinal L-cells with consequent peptide failure response to specific stimulation.
外源性胰高血糖素样肽1（GLP-1）的生物活性在2型糖尿病患者中得以保留，这使得该肽的给药主要通过其促胰岛素作用使血糖接近正常化。GLP-1还可降低1型糖尿病患者与进餐相关的胰岛素需求，这表明在两种糖尿病状态下肠-胰岛轴均受损。为了研究这种代谢功能障碍，我们评估了16例1型糖尿病患者（年龄 = 40.5±14岁，糖化血红蛋白[HbA1C] = 7.8±1.5%）、14例2型糖尿病患者（年龄 = 56.5±13岁，HbA1C = 8.1±1.8%）和10例匹配的对照者空腹及对营养摄入反应时的内源性GLP-1浓度。在吸收后状态下，给所有受试者给予一份混合早餐（230千卡），并在随后3小时内采集血样以测定血糖、胰岛素、C肽和GLP-1。在正常受试者中，试验餐可使GLP-1显著升高（30分钟、60分钟时：p<0.01），使该肽水平恢复至基础浓度。在2型糖尿病患者中，空腹血浆GLP-1与对照者相似（102.1±1.9对97.3±4.01皮克/毫升），但营养摄入未能使血浆肽水平升高，在试验期间甚至降低（p<0.01）。同样，1型糖尿病患者餐后GLP-1也未升高，尽管基础肽分泌得以维持（106.5±1.5皮克/毫升）。与对照者相比，试验餐在两组糖尿病患者中均在60分钟时使血浆胰高血糖素水平显著升高（p<0.01）。总之，无论是在胰岛素抵抗还是胰岛素缺乏的情况下，慢性高血糖作为两种代谢紊乱的共同特征，都可能导致肠L细胞逐渐脱敏，从而使肽对特定刺激的反应失效。
