Mouse Models of Type II Diabetes Mellitus in Drug Discovery
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.
Key wordsType II diabetes mellitus drug discovery glucose tolerance test insulin tolerance test insulin secretion insulin sensitivity diet-induced obesity leptin insulin NEFA
dual energy X-ray absorptiometry;
magnetic resonance imaging;
glucose-stimulated insulin secretion;
glucose tolerance test;
insulin tolerance test;
non-esterified fatty acid;
type II diabetes mellitus;
Dulbecco’s phosphate-buffered saline
dose providing 50% efficacy.
I am grateful to Jonitha Gardner, Laura Hoffman, Cheryl Loughery, Drs. Jiangwen Majeti, Alykhan Motani, and Wen-Chen Yeh for scientific discussions and critical review of the manuscript.
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