NIH experiment in centralized mouse phenotyping: the Vanderbilt experience and recommendations for evaluating glucose homeostasis in the mouse

Abstract

This article addresses two topics. We provide an overview of the National Institutes of Health Mouse Metabolic Phenotyping Center (MMPC) Program. We then discuss some observations we have made during the first eight years of the Vanderbilt MMPC regarding common phenotyping practices. We include specific recommendations to improve phenotyping practices for tests of glucose tolerance and insulin action. We recommend that methods for experiments in vivo be described in manuscripts. We make specific recommendations for data presentation, interpretation, and experimental design for each test. To facilitate and maximize the exchange of scientific information, we suggest that guidelines be developed for methods used to assess glucose tolerance and insulin action in vivo.

Disruption of Gpr45 causes reduced hypothalamic POMC expression and obesity

“…Since lean mass is the principal site of glucose disposal, caution is warranted when interpreting glucose metabolic data in these mutants, especially if the assays were performed based on the body weight (64). Gpr45 PB1/PB1 mice develop obesity along with reduced lean mass ( Figure 2H).…”

Fatty acid metabolism, energy expenditure and insulin resistance in muscle

“…Various technical considerations of glucose and insulin tolerance tests must be considered when discussing the metabolic implications of these tests for muscle insulin action. The timing and route of administration of glucose and duration of fast before glucose administration influence the results of glucose tolerance tests (Andrikopoulos et al 2008, McGuinness et al 2009, and our recent studies suggest that changes in glucose tolerance may reflect changes in lipid content and insulin action in the liver more than insulin action in muscle, especially in the initial stages of fat accumulation after starting a high-fat diet (Montgomery et al 2013. Insulin tolerance tests were devised largely to assess the effectiveness of counter-regulatory mechanisms in response to insulin-induced hypoglycaemia and therefore the utility of these tests to assess peripheral insulin action is debatable.…”

“…Insulin tolerance tests were devised largely to assess the effectiveness of counter-regulatory mechanisms in response to insulin-induced hypoglycaemia and therefore the utility of these tests to assess peripheral insulin action is debatable. This is particularly the case when conclusions about insulin effectiveness are related to glucose measurements in the later half of the test (30-90 min) when the injected insulin has largely been cleared or when there is a difference in basal glycaemia and results are expressed as % basal (McGuinness et al 2009). Neither glucose tolerance nor insulin tolerance tests give specific data regarding insulin effectiveness in muscle, although several methodological variations have used concurrent injection of radioactive tracers to assess glucose clearance into muscle during a glucose tolerance or insulin tolerance test (Crosson et al 2003.…”

11β-Hydroxysteroid dehydrogenase type 1 shRNA ameliorates glucocorticoid-induced insulin resistance and lipolysis in mouse abdominal adipose tissue

“…Twenty days following 11␤-HSD1 shRNA treatment, intraperitoneal insulin tolerance test (ITT) was performed on mice after an 8-h fast, and blood samples were drawn at different times following insulin injection (0.75 U/kg ip) (29). For the glucose tolerance test (GTT), mice were fasted on 21 days for 12 h, and blood samples were taken from a tail vein after the 1 g/kg glucose injection.…”