Overkamp Dietrich, Volk Annette, Maerker Elke, Heide Peter E, Wahl Hans G, Rett Kristian, Häring Hans U
Department of Internal Medicine IV, Tübingen, Germany.
Diabetes Care. 2002 Nov;25(11):2065-73. doi: 10.2337/diacare.25.11.2065.
This study addressed whether acute infusion of glimepiride influences glucose metabolism independent of its effect on insulin secretion.
Ten healthy, glucose-tolerant but insulin-resistant probands were subjected to a placebo-controlled, double-blind, cross-over study. Each individual received infusions of either 0.15 mol/l saline or glimepiride in randomized order on two separate occasions. A three-step hyperinsulinemic (0.5, 1.0, and 1.5 mU. kg(-1). min(-1))-euglycemic glucose clamp was performed on both occasions to determine insulin sensitivity. Glimepiride-induced insulin secretion was inhibited by octreotide. Endogenous glucose production and glucose elimination were measured with the "hot" glucose infusion method using U-[(13)C]glucose as tracer. Glucose oxidation was determined from indirect calorimetry. Lipolysis was evaluated by measurements of nonesterified fatty acid (NEFA) and glycerol concentration and measurement of glycerol production.
Plasma glucose and insulin concentrations were not significantly different between glimepiride or saline infusions. There was a significant increase in the rate of glucose infusion necessary to maintain euglycemia during infusion of glimepiride during the low- (12.2 +/- 1.1 vs. 16.1 +/- 1.7 micro mol. kg(-1). min(-1)) and intermediate-dose insulin infusion (24.4 +/- 1.7 vs. 30.0 +/- 2.8 micro mol. kg(-1). min(-1)). This was explained by an increased rate of glucose elimination and to a lesser degree by a decrease in glucose production. Glucose oxidation rate was not different. NEFA and glycerol concentration and glycerol production were equally suppressed.
Glimepiride improves peripheral glucose uptake and decreases endogenous glucose production independent of its insulin secretagogue action. The effects shown in this acute study are, however, too small to be considered therapeutically beneficial for the individual patient.
本研究探讨了急性输注格列美脲是否能在不依赖其对胰岛素分泌影响的情况下影响葡萄糖代谢。
对10名健康、糖耐量正常但胰岛素抵抗的受试者进行了一项安慰剂对照、双盲、交叉研究。每位受试者在两个不同的时间分别随机接受0.15mol/l生理盐水或格列美脲的输注。在这两种情况下均进行三步高胰岛素血症（0.5、1.0和1.5mU·kg⁻¹·min⁻¹）-正常血糖葡萄糖钳夹试验以确定胰岛素敏感性。奥曲肽抑制格列美脲诱导的胰岛素分泌。使用U-[(¹³)C]葡萄糖作为示踪剂，采用“热”葡萄糖输注法测量内源性葡萄糖生成和葡萄糖清除。通过间接量热法测定葡萄糖氧化。通过测量非酯化脂肪酸（NEFA）和甘油浓度以及甘油生成来评估脂解作用。
输注格列美脲或生理盐水期间，血浆葡萄糖和胰岛素浓度无显著差异。在低剂量（12.2±1.1对16.1±1.7μmol·kg⁻¹·min⁻¹）和中剂量胰岛素输注（24.4±1.7对30.0±2.8μmol·kg⁻¹·min⁻¹）期间，输注格列美脲时维持正常血糖所需的葡萄糖输注速率显著增加。这是由于葡萄糖清除率增加，在较小程度上是由于葡萄糖生成减少。葡萄糖氧化率没有差异。NEFA和甘油浓度以及甘油生成均受到同等程度的抑制。
格列美脲可改善外周葡萄糖摄取并减少内源性葡萄糖生成，且不依赖其促胰岛素分泌作用。然而，这项急性研究中显示的效应过小，对个体患者不具有治疗益处。
