Mouse Models of Type 2 Diabetes Mellitus in Drug Discovery

  • Helene BaribaultEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1438)


Type 2 diabetes is a fast-growing epidemic in industrialized countries, associated with obesity, lack of physical exercise, aging, family history, and ethnic background. Diagnostic criteria are elevated fasting or postprandial blood glucose levels, a consequence of insulin resistance. Early intervention can help patients to revert the progression of the disease together with lifestyle changes or monotherapy. Systemic glucose toxicity can have devastating effects leading to pancreatic beta cell failure, blindness, nephropathy, and neuropathy, progressing to limb ulceration or even amputation. Existing treatments have numerous side effects and demonstrate variability in individual patient responsiveness. However, several emerging areas of discovery research are showing promises with the development of novel classes of antidiabetic drugs.

The mouse has proven to be a reliable model for discovering and validating new treatments for type 2 diabetes mellitus. We review here commonly used methods to measure endpoints relevant to glucose metabolism which show good translatability to the diagnostic of type 2 diabetes in humans: baseline fasting glucose and insulin, glucose tolerance test, insulin sensitivity index, and body type composition. Improvements on these clinical values are essential for the progression of a novel potential therapeutic molecule through a preclinical and clinical pipeline.

Key words

Type 2 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


Diet-induced obesity


Dulbecco’s Phosphate Buffered Saline


Dose providing 50 % efficacy


Glucose-stimulated insulin secretion


Glucose tolerance test






Insulin tolerance test


Magnetic Resonance Imaging


Nonesterified fatty acid


per oral gavage










Type 2 diabetes mellitus



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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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Ardelyx Inc.FremontUSA

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