Courtney C H, Atkinson A B, Ennis C N, Sheridan B, Bell P M
Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, UK.
Metabolism. 2003 Aug;52(8):1050-5. doi: 10.1016/s0026-0495(03)00156-2.
Insulin is normally secreted in man in regular pulses every 5 to 15 minutes. Disordered pulsation has been demonstrated in several insulin-resistant states and it is unclear whether this represents a primary beta-cell defect contributing to impairment of peripheral insulin action or rather is a consequence of insulin resistance. Basal or near basal insulin administration by pulsatile infusion augments hypoglycemic effect and improves insulin-mediated glucose uptake compared with insulin by continuous infusion. To date no study has examined whether normal basal insulin pulsatility is required to preserve subsequent insulin sensitivity during hyperinsulinemia. We studied the effect of overnight pulsatile versus continuous basal insulin on a subsequent hyperinsulinemic euglycemic clamp. Nineteen normal volunteers (male:female ratio, 17:2; mean age +/- SEM, 26.1 +/- 2.3 years) were studied on 2 occasions each. Endogenous insulin secretion was inhibited by octreotide (0.43 microg kg(-1). h(-1)) and replaced overnight at 5.4 mU kg(-1). h(-1) either by continuous infusion or in 2-minute pulses every 13 minutes (n = 10) or every 7 minutes (n = 9). Glucagon was replaced at physiological concentration by continuous infusion (30 ng. kg(-1). h(-1)). Venous plasma glucose overnight was not significantly different between the pulsatile and continuous protocols. After discontinuing the overnight insulin infusion, insulin action was assessed during a hyperinsulinemic euglycemic clamp (1 mU kg(-1). h(-1)). Glucose infusion rates at steady-state during the hyperinsulinemic clamp were similar between continuous and both frequencies of pulsatile infusion (continuous 44.6 +/- 4.3 micromol. kg(-1). min(-1) v 13-minute pulsatile 41.7 +/- 5.9 micromol. kg(-1). min(-1), P =.27; continuous 34.6 +/- 2.5 micromol. kg(-1) min(-1) v 7-minute pulsatile 41.4 +/- 3.2 micromol. kg(-1). min(-1), P =.08). We conclude that overnight pulsatile compared with continuous insulin administration has no different effect on subsequent peripheral insulin-mediated glucose uptake. A priming effect cannot therefore explain the previously demonstrated association between endogenous insulin pulse frequency and peripheral insulin action.
在人类中，胰岛素通常每隔5至15分钟以规律的脉冲形式分泌。在几种胰岛素抵抗状态下已证实存在脉冲分泌紊乱，目前尚不清楚这是导致外周胰岛素作用受损的原发性β细胞缺陷，还是胰岛素抵抗的结果。与持续输注胰岛素相比，通过脉冲输注给予基础或接近基础量的胰岛素可增强降糖效果并改善胰岛素介导的葡萄糖摄取。迄今为止，尚无研究探讨在高胰岛素血症期间维持后续胰岛素敏感性是否需要正常的基础胰岛素脉冲分泌。我们研究了过夜脉冲式与持续基础胰岛素对随后高胰岛素正常血糖钳夹试验的影响。对19名正常志愿者（男女比例为17:2；平均年龄±标准误，26.1±2.3岁）每人进行了2次研究。用奥曲肽（0.43μg·kg⁻¹·h⁻¹）抑制内源性胰岛素分泌，并在夜间以5.4mU·kg⁻¹·h⁻¹的剂量进行替代，替代方式为持续输注或每13分钟（n = 10）或每7分钟（n = 9）进行一次2分钟的脉冲输注。通过持续输注（30ng·kg⁻¹·h⁻¹）将胰高血糖素替代至生理浓度。在脉冲式和持续输注方案之间，夜间静脉血浆葡萄糖无显著差异。在停止过夜胰岛素输注后，在高胰岛素正常血糖钳夹试验（1mU·kg⁻¹·h⁻¹）期间评估胰岛素作用。在高胰岛素钳夹试验期间，持续输注与两种频率的脉冲输注的稳态葡萄糖输注率相似（持续输注44.6±4.3μmol·kg⁻¹·min⁻¹对13分钟脉冲输注41.7±5.9μmol·kg⁻¹·min⁻¹，P = 0.27；持续输注34.6±2.5μmol·kg⁻¹·min⁻¹对7分钟脉冲输注41.4±3.2μmol·kg⁻¹·min⁻¹，P = 0.08）。我们得出结论，与持续胰岛素给药相比，过夜脉冲式给药对随后外周胰岛素介导的葡萄糖摄取没有不同影响。因此，启动效应无法解释先前证明的内源性胰岛素脉冲频率与外周胰岛素作用之间的关联。
