Diabetes and Transcription Factors Group, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia.
Curr Mol Med. 2013 Jan;13(1):126-39.
Type 2 diabetes (T2D) is a metabolic disorder characterised by the inability of β-cells to secrete enough insulin to maintain glucose homeostasis. Pancreatic β-cells secrete insulin in a biphasic manner, first and second phase insulin secretion, and loss of first phase insulin secretion is an independent predictor of T2D onset. Restoration of first phase insulin secretion has been shown to improve blood glucose in T2D by suppressing hepatic glucose production and priming insulin sensitive tissue to more readily take up glucose and has thus prompted numerous studies into its regulation. First phase insulin secretion is initiated primarily by the classical triggering pathway, a complex system comprised of multiple stimulatory signals. Recent studies have identified a number of novel regulatory factors that are crucial for first phase insulin secretion and glucose homeostasis. These include, among others, hypoxia inducible factor 1α, von Hippel-Lindau, factor inhibiting HIF, nicotinamide phospho-ribosyl-transferase, and the sirtuin family. This review will outline how first phase insulin secretion is initiated and detail some of the recent findings in its regulation.
2 型糖尿病（T2D）是一种代谢紊乱，其特征是β细胞无法分泌足够的胰岛素来维持葡萄糖稳态。胰腺β细胞以双相方式分泌胰岛素，即第一相和第二相胰岛素分泌，第一相胰岛素分泌的丧失是 T2D 发病的独立预测因素。恢复第一相胰岛素分泌已被证明通过抑制肝葡萄糖生成来改善 T2D 的血糖，并使胰岛素敏感组织更容易摄取葡萄糖，因此促使人们对其调节进行了大量研究。第一相胰岛素分泌主要由经典触发途径启动，该途径是一个由多个刺激信号组成的复杂系统。最近的研究确定了一些对第一相胰岛素分泌和葡萄糖稳态至关重要的新调节因子。其中包括缺氧诱导因子 1α、冯·希佩尔-林道、抑制 HIF 的因子、烟酰胺磷酸核糖转移酶和沉默调节蛋白家族。这篇综述将概述第一相胰岛素分泌是如何启动的，并详细介绍其调节的一些最新发现。
