The development of new therapies for the treatment of type 2 diabetes requires robust, reproducible and well validated in vivo experimental systems. Mice provide the most ideal animal model for studies of potential therapies. Unlike larger animals, mice have a short gestational period, are genetically similar, often give birth to many offspring at once and can be housed as multiple groups in a single cage. The mouse model has been extensively metabolically characterized using different tests. This report summarizes how these tests can be executed and how arising data are analyzed to confidently determine changes in insulin resistance and insulin secretion with high reproducibility. The main tests for metabolic assessment in the mouse reviewed here are the glucose clamp, the intravenous and the oral glucose tolerance tests. For all these experiments, including some commonly adopted variants, we describe: (i) their performance; (ii) their advantages and limitations; (iii) the empirical formulas and mathematical models implemented for the analysis of the data arising from the experimental procedures to obtain reliable measurements of peripheral insulin sensitivity and beta cell function. Finally, a list of previous applications of these methods and analytical techniques is provided to better comprehend their use and the evidences that these studies yielded. 1. Introduction The global incidence of type 2 diabetes is predicted to grow rapidly also in the coming decades as more countries develop economically and overweight and obesity spread to populations with a genetic predisposition to the development of the disease [1]. These factors make the need for effective diabetes therapies that much greater. The development of new therapies for the treatment of type 2 diabetes requires robust, reproducible, and well validated in vivo experimental systems. Of particular importance are preclinical in vivo models, since these may select and refine experimental models for further studies and drug development in humans. There are multiple animal models of insulin resistance and decreased beta cell function including genetically deficient mice and rats as well as mouse and rat strains fed a high energy diet. Mice may provide the most ideal animal model for studies of potential type 2 diabetes therapies. Unlike larger animals, mice have a short gestational period, often give birth to many offspring at once, and can be housed in multiple groups in a single cage. This makes “in house” breeding less expensive and makes it easier to generate larger numbers to obtain
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