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.
Baribault
Helene
H
Department of Metabolic Disorders, Amgen, South San Francisco, CA, USA.
D000818:Animals; D001823:Body Composition; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics; D004195:Disease Models, Animal; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose