School of Food and Nutrition Sciences, Jomo Kenyatta University of Agriculture and Technology, P. O. Box 62000, 00200 Nairobi, Kenya.
Oxid Med Cell Longev. 2020 Jul 21;2020:3089139. doi: 10.1155/2020/3089139. eCollection 2020.
Glucagon, a hormone secreted by pancreatic alpha cells, contributes to the maintenance of normal blood glucose concentration by inducing hepatic glucose production in response to declining blood glucose. However, glucagon hypersecretion contributes to the pathogenesis of type 2 diabetes. Moreover, diabetes is associated with relative glucagon undersecretion at low blood glucose and oversecretion at normal and high blood glucose. The mechanisms of such alpha cell dysfunctions are not well understood. This article reviews the genesis of alpha cell dysfunctions during the pathogenesis of type 2 diabetes and after the onset of type 1 and type 2 diabetes. It unravels a signaling pathway that contributes to glucose- or hydrogen peroxide-induced glucagon secretion, whose overstimulation contributes to glucagon dysregulation, partly through oxidative stress and reduced ATP synthesis. The signaling pathway involves phosphatidylinositol-3-kinase, protein kinase B, protein kinase C delta, non-receptor tyrosine kinase Src, and phospholipase C gamma-1. This knowledge will be useful in the design of new antidiabetic agents or regimens.
胰高血糖素是一种由胰岛α细胞分泌的激素，通过响应血糖下降促进肝糖生成，有助于维持正常的血糖浓度。然而，胰高血糖素分泌过多会导致 2 型糖尿病的发病机制。此外，糖尿病与低血糖时相对胰高血糖素分泌不足以及正常和高血糖时分泌过多有关。这种α细胞功能障碍的机制尚不清楚。本文综述了 2 型糖尿病发病过程中和 1 型和 2 型糖尿病发病后α细胞功能障碍的发生机制。本文揭示了一条参与葡萄糖或过氧化氢诱导胰高血糖素分泌的信号通路，其过度刺激导致胰高血糖素失调，部分原因是氧化应激和 ATP 合成减少。该信号通路涉及磷脂酰肌醇-3-激酶、蛋白激酶 B、蛋白激酶 C 德尔塔、非受体酪氨酸激酶Src 和磷脂酶 C 伽马-1。这些知识将有助于设计新的抗糖尿病药物或方案。
