Baribault Helene
Department of Metabolic Disorders, Amgen, South San Francisco, CA, USA.
Methods Mol Biol. 2010;602:135-55. doi: 10.1007/978-1-60761-058-8_9.
Type II diabetes is a fast-growing epidemic in industrialized countries. Many recent advances have led to the discovery and marketing of efficient novel therapeutic medications. Yet, because of side effects of these medications and the variability in individual patient responsiveness, unmet needs subsist for the discovery of new drugs. The mouse has proven to be a reliable model for discovering and validating new treatments for type II diabetes mellitus. We review here the most common mouse models used for drug discovery for the treatment of type II diabetes. The methods presented focus on measuring the equivalent end points in mice to the clinical values of glucose metabolism used for the diagnostic of type II diabetes in humans: i.e., baseline fasting glucose and insulin, glucose tolerance test, and insulin sensitivity index. Improvements on these clinical values are essential for the progression of a novel potential therapeutic molecule through a preclinical and clinical pipeline.
在工业化国家，2型糖尿病正迅速蔓延。最近的许多进展促使了高效新型治疗药物的发现和上市。然而，由于这些药物的副作用以及个体患者反应的差异，新药研发仍存在未满足的需求。事实证明，小鼠是发现和验证2型糖尿病新疗法的可靠模型。在此，我们回顾用于2型糖尿病治疗药物研发的最常见小鼠模型。所介绍的方法着重于测量小鼠中与用于诊断人类2型糖尿病的葡萄糖代谢临床值相当的终点指标，即基线空腹血糖和胰岛素、葡萄糖耐量试验以及胰岛素敏感性指数。对于一种新型潜在治疗分子在临床前和临床流程中的进展而言，改善这些临床值至关重要。
