Disorders of glucose metabolism, e.g. type 2 diabetes mellitus, are important widespread diseases today. The hypothesis-driven Glucose Metabolism pipeline mainly focusses on the in-vivo characterization of mouse models with altered glucose metabolism on the whole-body level. It comprises several phenotyping test assays addressing gene functions linked to glucose metabolism in mice. Fasting or fed hyper- or hypoglycemia, altered glucose tolerance, and differences in insulin sensitivity respectively insulin secretion, are the major endpoints of the Glucose Metabolism pipeline.
To address these aspects in mouse models the following tests are applied: Blood levels of glucose, lipids and relevant hormones in fed and fasting state are determined at defined time points during the workflow. Analysis of blood or plasma samples also includes biomarkers that are needed to examine organ function or damage. Changes in body mass and body composition are important indicators for effects on systemic energy balance regulation. Therefore we measure body mass and body composition based on quantitative NMR. To identify specific alterations in the response to a glucose load, a glucose tolerance test is performed. Since observed differences in glucose tolerance can be due to several reasons, for example altered production, maturation, secretion, or structure of insulin on the one hand or insulin resistance of tissues on the other hand, additional tests, such as the insulin tolerance test, provide important additional insight. In detail, an insulin tolerance test monitors blood glucose levels in response to insulin injection as an indicator of whole body insulin sensitivity. Finally, glucose clamps are conducted. Clamp studies are the gold standard to investigate β-cell function (insulin secretion) or insulin action (glucose metabolism on the whole-body or organ level). Two different clamp types are usually applied: (1) hyperglycemic clamp to address insulin secretion and (2) the hyperinsulinemic-euglycemic clamp to address glucose uptake in tissues. In addition, the clamp set up allows measuring tissue specific glucose uptake rates by tracing labelled glucose. In addition to the test assays of this pipeline, blood glucose and insulin levels can regularly be monitored (e.g. every two weeks) to investigate temporal dynamics or age-related changes.