ANTIDIABETOGENIC EFFECT OF GLUCAGON-LIKE PEPTIDE-1 (7-36)AMIDE IN NORMAL SUBJECTS AND PATIENTS WITH DIABETES-MELLITUS
ANTIDIABETOGENIC EFFECT OF GLUCAGON-LIKE PEPTIDE-1 (7-36)AMIDE IN NORMAL SUBJECTS AND PATIENTS WITH DIABETES-MELLITUS
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DOI：
10.1056/nejm199205143262003
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发表时间：
1992-05-14
影响因子：
158.5
通讯作者：
EFENDIC, S
中科院分区：
文献类型：
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作者：
GUTNIAK, M;ORSKOV, C;EFENDIC, S
背景胰高血糖素样肽-1（7-36）酰胺（胰高血糖素样促胰岛素肽，或GLIP）是一种胃肠道肽，可增强生理浓度胰岛素的释放。其对糖尿病患者的影响尚不清楚。我们比较了8名正常受试者、9名非胰岛素依赖型糖尿病（NIDDM）肥胖患者和8名胰岛素依赖型糖尿病（IDDM）患者输注GLIP（使血浆GLIP浓度升高2倍）与输注生理盐水对餐后胰岛素、胰高血糖素和生长抑素释放的影响。在输注每种药物期间，通过闭环胰岛素输注系统（人工胰腺）控制糖尿病患者的血糖浓度，从而可以测量与膳食相关的外源性胰岛素需求。在胰岛素依赖型糖尿病患者中，在输注GLIP和生理盐水期间进行正糖钳夹研究，以确定GLIP对胰岛素敏感性的影响。在正常受试者中，输注GLIP显著降低了血糖浓度（P < 0.01）和胰岛素和胰高血糖素血浆浓度（两种比较均P < 0.05）的进餐相关升高。胰岛素生成指数（胰岛素与葡萄糖的比率）增加了近10倍，表明GLIP具有促胰岛素作用。在NIDDM患者中，输注GLIP使计算的平均（+/- SE）异糖基化膳食相关胰岛素需求量从17.4 +/- 2.8降至2.0 +/- 0.5 U（P < 0.001），因此，尽管刺激了胰岛素释放，血浆游离胰岛素的曲线下积分面积仍降低（P < 0.05）。在IDDM患者中，GLIP输注将计算的异甘草酸餐相关胰岛素需求量从9.4 +/- 1.5降至4.7 +/- 1.4 U。肽减少胰高血糖素和生长抑素释放在两组患者。在胰岛素依赖型糖尿病患者的正常血糖钳夹研究中，GLIP输注显著增加了葡萄糖利用率（生理盐水vs. GLIP，7.2 +/- 0.5 vs. 8.6 +/- 0.4 mg/kg体重/min; P < 0.01）。GLIP具有抗糖尿病的作用，因此它可能是有用的治疗NIDDM患者。
Background. Glucagon-like peptide-1 (7-36) amide (glucagon-like insulinotropic peptide, or GLIP) is a gastrointestinal peptide that potentiates the release of insulin in physiologic concentrations. Its effects in patients with diabetes mellitus are not known.Methods. We compared the effect of an infusion of GLIP that raised plasma concentrations of GLIP twofold with the effect of an infusion of saline, on the meal-related release of insulin, glucagon, and somatostatin in eight normal subjects, nine obese patients with non-insulin-dependent diabetes mellitus (NIDDM), and eight patients with insulin-dependent diabetes mellitus (IDDM). The blood glucose concentrations in the patients with diabetes were controlled by a closed-loop insulin-infusion system (artificial pancreas) during the infusion of each agent, allowing measurement of the meal-related requirement for exogenous insulin. In the patients with IDDM, normoglycemic-clamp studies were performed during the infusions of GLIP and saline to determine the effect of GLIP on insulin sensitivity.Results. In the normal subjects, the infusion of GLIP significantly lowered the meal-related increases in the blood glucose concentration (P < 0.01) and the plasma concentrations of insulin and glucagon (P < 0.05 for both comparisons). The insulinogenic index (the ratio of insulin to glucose) increased almost 10-fold, indicating that GLIP had an insulinotropic effect. In the patients with NIDDM, the infusion of GLIP reduced the mean (+/- SE) calculated isoglycemic meal-related requirement for insulin from 17.4 +/- 2.8 to 2.0 +/- 0.5 U (P < 0.001), so that the integrated area under the curve for plasma free insulin was decreased (P < 0.05) in spite of the stimulation of insulin release. In the patients with IDDM, the GLIP infusion decreased the calculated isoglycemic meal-related insulin requirement from 9.4 +/- 1.5 to 4.7 +/- 1.4 U. The peptide decreased glucagon and somatostatin release in both groups of patients. In the normoglycemic-clamp studies in the patients with IDDM, the GLIP infusion significantly increased glucose utilization (saline vs. GLIP, 7.2 +/- 0.5 vs. 8.6 +/- 0.4 mg per kilogram of body weight per minute; P < 0.01).Conclusions. GLIP has an antidiabetogenic effect, and it may therefore be useful in the treatment of patients with NIDDM.