Schmitz Ole, Rungby Joergen, Edge Linda, Juhl Claus B
Department of Diabetes, University Hospital of Aarhus and Institute of Pharmacology, University of Aarhus, 8000 Aarhus C, Denmark.
Ageing Res Rev. 2008 Dec;7(4):301-5. doi: 10.1016/j.arr.2008.04.002. Epub 2008 May 3.
Insulin is released in a pulsatile manner, which results in oscillatory concentrations in blood. The oscillatory secretion improves release control and enhances the hormonal action. Insulin oscillates with a slow ultradian periodicity (approximately 140 min) and a high-frequency periodicity (approximately 6-10 min). Only the latter is reviewed in this article. At least 75% of the insulin secretion is released in a pulsatile manner. Individuals prone to developing diabetes or with overt type 2 diabetes are characterized by irregular oscillations of plasma insulin. Many factors have impact on insulin pulsatility such as age, insulin resistance and glycemic level. In addition, tiny glucose oscillations are capable of entraining insulin oscillations in healthy people in contrast to type 2 diabetic individuals emphasizing a profound disruption of the beta-cells in type 2 diabetes to sense or respond to physiological glucose excursions. A crucial question is how approximately 1,000,000 islets, each containing from a few to several thousand beta-cells, can be coordinated to secrete insulin in a pulsatile manner. This is blatantly a very complex operation to control involving an intra-pancreatic neural network, an intra-islet communication and metabolic oscillations in the beta-cell itself. Overnight beta-cell rest, e.g. during somatostatin administration, improves the disordered pulsatile insulin secretion in type 2 diabetes. Acute as well as long-term administration of sulphonylureas (SU) leads to substantial amplification (approximately 50%) of the pulsatile insulin secretion in type 2 diabetes. This is probably cardinal in terms of governing the hepatic glucose release in type 2 diabetes. Whether sulfonylureas also improve the ability of the beta-cells to sense glucose fluctuations remains to be explored. Thiazolidinediones reduce the pulsatile insulin secretion without affecting regularity, but appear to improve the ability of the beta-cell to be entrained by small glucose excursions. Finally, similar to SUs, the incretin hormone GLP-1 also results in an augmented pulsatile burst mass in both healthy and diabetic individuals, in the latter group, however, without influencing the disorderliness of pulses. This review will briefly describe the high-frequency insulin pulsatility during physiologic and pathophysiologic conditions as well as the influence of some hypoglycemic compounds on the insulin oscillations.
胰岛素以脉冲方式释放，这导致血液中胰岛素浓度呈振荡变化。振荡分泌改善了释放控制并增强了激素作用。胰岛素以缓慢的超日周期（约140分钟）和高频周期（约6 - 10分钟）振荡。本文仅综述后者。至少75%的胰岛素分泌以脉冲方式释放。易患糖尿病或患有显性2型糖尿病的个体，其血浆胰岛素振荡不规则。许多因素会影响胰岛素的脉冲性，如年龄、胰岛素抵抗和血糖水平。此外，与2型糖尿病患者不同，微小的葡萄糖振荡能够在健康个体中引发胰岛素振荡，这强调了2型糖尿病中β细胞感知或响应生理性葡萄糖波动的能力存在严重破坏。一个关键问题是，每个包含从几个到几千个β细胞的约100万个胰岛如何协同以脉冲方式分泌胰岛素。这显然是一个非常复杂的控制操作，涉及胰腺内神经网络、胰岛内通讯以及β细胞自身的代谢振荡。夜间β细胞休息，例如在使用生长抑素期间，可改善2型糖尿病中紊乱的脉冲式胰岛素分泌。磺脲类药物（SU）的急性和长期给药会使2型糖尿病患者的脉冲式胰岛素分泌大幅增加（约50%）。这在控制2型糖尿病患者肝脏葡萄糖释放方面可能至关重要。磺脲类药物是否还能改善β细胞感知葡萄糖波动的能力仍有待探索。噻唑烷二酮类药物可减少脉冲式胰岛素分泌但不影响其规律性，不过似乎能改善β细胞被小幅度葡萄糖波动引发振荡的能力。最后，与磺脲类药物类似，肠促胰岛素激素胰高糖素样肽 - 1（GLP - 1）在健康个体和糖尿病个体中均会导致脉冲式爆发量增加，然而在后者组中，它不会影响脉冲的紊乱程度。本综述将简要描述生理和病理生理条件下的高频胰岛素脉冲性以及一些降糖化合物对胰岛素振荡的影响。
