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Methods Mol Biol. 2016;1438:153-75. doi: 10.1007/978-1-4939-3661-8_10.

Mouse Models of Type 2 Diabetes Mellitus in Drug Discovery.

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1
Ardelyx Inc., 34175 Ardenwood Blvd, Suite 200, Fremont, CA, 94555, USA. baribaulth@gmail.com.

Abstract

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.

KEYWORDS:

Diet-induced obesity; Drug discovery; Glucose tolerance test; Insulin; Insulin secretion; Insulin sensitivity; Insulin tolerance test; Leptin; NEFA; Type 2 diabetes mellitus

PMID:
27150090
DOI:
10.1007/978-1-4939-3661-8_10
[Indexed for MEDLINE]

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