Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes.
Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes.
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DOI：
10.1016/j.mam.2015.01.003
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发表时间：
2015-04
影响因子：
10.6
通讯作者：
Sherman AS
中科院分区：
文献类型：
--
作者：
Satin LS;Butler PC;Ha J;Sherman AS
2型糖尿病（T2DM）发生时，β细胞功能和/或质量的增加不能补偿胰岛素抵抗的增加。大量研究表明，在葡萄糖耐受不良的发展过程中，代谢的纵向变化会导致2型糖尿病。然而，胰岛素分泌量和时间模式的变化所起的作用尚未得到充分研究。胰腺β细胞分泌的大部分胰岛素以搏动模式释放，在T2DM中被破坏。在此，我们回顾了人类从葡萄糖耐受不良到2型糖尿病进展过程中β细胞搏动性变化的证据，并对该疾病的病因有重要影响。我们回顾了胰岛素搏动性提高分泌胰岛素对其靶点的功效的证据，特别是肝脏葡萄糖产生，但也检查了搏动性改变或被周围葡萄糖摄取改变的证据。最后，我们总结了目前对胰岛素分泌振荡的生物物理机制的理解。了解胰岛素搏动如何促进正常的葡萄糖稳态和代谢疾病状态的改变可能有助于改善T2DM的治疗。
Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM.