Ashcroft Frances M, Lloyd Matthew, Haythorne Elizabeth A
Department of Physiology, Anatomy and Genetics, Parks Road, Oxford, OX1 3PT, UK.
Department of Physiology, Anatomy and Genetics, Parks Road, Oxford, OX1 3PT, UK.
Trends Endocrinol Metab. 2023 Feb;34(2):119-130. doi: 10.1016/j.tem.2022.12.007. Epub 2022 Dec 29.
Type 2 diabetes (T2D) is a global health problem characterised by chronic hyperglycaemia due to inadequate insulin secretion. Because glucose must be metabolised to stimulate insulin release it was initially argued that drugs that stimulate glucokinase (the first enzyme in glucose metabolism) would enhance insulin secretion in diabetes. However, in the long term, glucokinase activators have been largely disappointing. Recent studies show it is hyperactivation of glucose metabolism, not glucose itself, that underlies the progressive decline in beta-cell function in diabetes. This perspective discusses if glucokinase activators exacerbate this decline (by promoting glucose metabolism) and, counterintuitively, if glucokinase inhibitors might be a better therapeutic strategy for preserving beta-cell function in T2D.
2型糖尿病（T2D）是一个全球性的健康问题，其特征是由于胰岛素分泌不足导致慢性高血糖。由于葡萄糖必须被代谢以刺激胰岛素释放，最初有人认为刺激葡萄糖激酶（葡萄糖代谢中的第一种酶）的药物会增强糖尿病患者的胰岛素分泌。然而，从长期来看，葡萄糖激酶激活剂在很大程度上令人失望。最近的研究表明，是葡萄糖代谢的过度激活而非葡萄糖本身，是糖尿病中β细胞功能逐渐衰退的基础。本文探讨了葡萄糖激酶激活剂是否会加剧这种衰退（通过促进葡萄糖代谢），以及与直觉相反的是，葡萄糖激酶抑制剂是否可能是保护T2D患者β细胞功能的更好治疗策略。
