1 The Department of Science, Systems and Models, Roskilde University
This chapter deals with type 2 diabetes in vivo models and techniques suitable for testing new anti-diabetic compounds. In particular, the testing of TRP antagonist for beneficial effects against type 2 diabetes is considered. There are many choices of both in vitro techniques and in vivo models and in principle they can be combined in various ways. The comprehensive listing of all relevant tests and models is too long to be discussed and described in detail here. Therefore, a few selected in vivo experiments (author's models of choice) are described. These are acute experiments after single dose of the TRP antagonist in rodents and could/should be repeated after chronic dosing. Non-rodent models are briefly discussed, and a single model and test are suggested but not described in detail. The experiments are aiming at demonstrating that the TRP antagonists are effective in treating hyperglycemia, impaired glucose tolerance, impaired insulin secretion, and insulin resistance in vivo and should, thus, be sufficient to demonstrate preclinical proof of concept of a TRP antagonist in type 2 diabetes in rodents. The experiments are suggestions and could be replaced or supplemented by others.
Methods in Pharmacology and Toxicology, 2012, p. 319-332