Metabolic Disorders: Glucose Tolerance Test
The Glucose Tolerance Test (GTT) is the standard for defining impaired glucose homeostasis in mammals. For example, intraperitoneal GTTs showed improved glucose clearance and the serum glucose and insulin levels were significantly lower in protein tyrosine phosphatase-1B (PTP-1B) and SHIP2 knockout mice (Klaman et al. 2000; Clement et al., 2001). These findings indicate improved insulin sensitivity, a possibility that was confirmed by hyperinsulinemic-euglycemic clamp studies in the PTP-1B knockout mice (Klaman et al., 2000). These results suggest that these two proteins are potential targets for new therapeutics aimed at Type II diabetes. In addition, the ability of retinoid X receptor agonists to lower serum glucose and insulin levels has been used as evidence that these agonists act as insulin sensitizers in vivo (Mukherjee et al., 1997). These examples validate the effectiveness of GTT for the identification of potential targets for diabetes.
GTTs are performed using a Lifescan Glucometer (LifeScan, Inc; Milpitas, CA). A fasting blood sample is taken before a bolus of glucose is administered. Animals are either injected intraperitoneally with 2 g/kg D-glucose delivered as a 20% solution (ipGTT) or oral gavaged with 10% of body weight of 20% glucose (oralGTT), and blood glucose levels are measured at 0, 30, 60, and 90 min after injection (Klaman LD et al., 2000).
Displayed below is a sample graph of how GTT observations are presented. In comprehensive phenotypic data packages graphs are interactive. Raw or calculated data and statistics can be seen by clicking on points in the graph.
Figure illustrates blood glucose levels before and 30, 60, or 90 minutes after receiving oral glucose (10% of body weight of 20% glucose solution). Blood glucose values of wild type littermates (green circle), homozygous (red diamond), and recent historical wild type (purple line) mice are plotted against long-term historical values (± 2 standard deviations) for wild type animals (green shading). Recent wild type values are calculated from data collected within 60 days of current measures and long-term historical values are derived from data collected on more than 10,000 wild type mice.
Clement S, Krause U, Desmedt F, Tanti JF, Behrends J, Pesesse X, Sasaki T, et al. (2001) The lipid phosphatase SHIP2 controls insulin sensitivity, Nature, 409:92-97.
Klaman LD, Boss O, Peroni OD, Kim JK, Martino JL, Zabolotny JM, Moghal N, et al. (2000) Increased energy expenditure, decreased adiposity, and tissue specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice, Mol Cell Biol, 20:5479-5489.
Mukherjee R, Davies PJ, Crombie DL, Bischoff ED, Cesario RM, Jow L, Hamann LG, Boehm MF, Mondon CE, Nadzan AM, Paterniti JR Jr, Heyman RA. (1997) Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists, Nature, 386(6623):407-10.