Mouse Models of Type II Diabetes Mellitus in Drug Discovery

  • Helene Baribault
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 602)

Abstract

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 words

Type II diabetes mellitus drug discovery glucose tolerance test insulin tolerance test insulin secretion insulin sensitivity diet-induced obesity leptin insulin NEFA 

Abbreviations

DEXA

dual energy X-ray absorptiometry;

MRI

magnetic resonance imaging;

DIO

diet-induced obesity;

GSIS

glucose-stimulated insulin secretion;

GTT

glucose tolerance test;

ITT

insulin tolerance test;

NEFA

non-esterified fatty acid;

T2DM

type II diabetes mellitus;

D-PBS

Dulbecco’s phosphate-buffered saline

STZ

streptozotocin;

PK

pharmacokinetics;

PD

pharmacodynamics;

ED50

dose providing 50% efficacy.

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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Helene Baribault
    • 1
  1. 1.Department of Metabolic DisordersAmgenSouth San FranciscoUSA

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