Delayed response of insulin-stimulated fluorine-18 deoxyglucose uptake in glucose transporter-4-null mice hearts
Marcus V. Simões, MD, PhD*,*,
Silvia Egert, PhD*,
Sibylle Ziegler, PhD*,
Masao Miyagawa, MD, PhD*,
Sybille Reder, BS*,
Terry Lehner, BS*,
Ngoc Nguyen, BS*,
Maureen J. Charron, PhD and
Markus Schwaiger, MD*
* Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA
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Figure 1 Western blot analysis of heart tissue for GLUT4 and GLUT1 proteins. As expected, there is an absence of the GLUT4 protein in homozygous (–/–) GLUT4-null mice. The GLUT1 protein displays a twofold increase in GLUT4-null mice (–/–) compared with wild-type mice (+/+). GLUT = glucose transporter.
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Figure 2 Representative positron emission tomography images obtained in wild-type and GLUT4-null mice under each of the experimental conditions. At baseline, no myocardial [18F]-2-deoxy-2-fluoro-D-glucose (FDG) activity was detected in the cardiac area of either animal. After simultaneous injection of insulin and FDG, the wild-type mouse presented with increased radiotracer uptake in the cardiac area (arrow), whereas no activity was identifiable in the GLUT4-null mouse. After 60 min, both animals had conspicuous myocardial FDG uptake of comparable intensity. GLUT = glucose transporter.
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Figure 3 Bar graphs summarizing the mean data of myocardial [18F]-2-deoxy-2-fluoro-D-glucose (FDG) uptake in GLUT4-null and wild-type mice (expressed as standard uptake values [SUVs], y-axis), using quantitative analysis of (A) in vivo positron emission tomography imaging and (B) in vitro gamma-counter tissue biodistribution studies. The positron emission tomography study was performed under the following conditions: baseline, simultaneous injection of insulin and FDG, and 60-min delay. The gamma-counter biodistribution study provides a more detailed time course of insulin-stimulated FDG uptake as 30-min and 120-min delay times points were also investigated. *p < 0.05 for comparisons with baseline values. p < 0.05 for comparisons between GLUT4-null and wild-type animals in each experimental condition. GLUT = glucose transporter.
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Figure 4 Examples of [18F]-2-deoxy-2-fluoro-D-glucose (FDG) time-activity curves obtained in isolated heart perfusion, using external coincidence detectors. This approach allows the evaluation of insulin-stimulated myocardial FDG uptake without the influence of systemic factors. (A) Short-term insulin effect: compared with the initial portion of the curve (baseline), an increase of the FDG uptake rate (slope of the curve segment) is seen in the wild-type mouse heart shortly after insulin is added to the perfusion buffer (arrow). Conversely, no change is observed in the GLUT4-null mouse heart after the addition of insulin (arrow). (B) Long-term insulin stimulation: hearts were perfused with insulin containing buffer 60 min after in vivo administration of insulin/glucose. In this condition, both GLUT4-null and wild-type hearts had an increased FDG uptake rate compared with the corresponding baseline value. GLUT = glucose transporter.
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Figure 5 Bar graph summarizing the mean data of the [18F]-2-deoxy-2-fluoro-D-glucose (FDG) uptake rate (expressed as ml/g/min, y-axis) obtained in isolated perfused hearts from GLUT4-null and wild-type mice in each of the experimental conditions (x-axis). *p < 0.05 for comparison with baseline. p < 0.05 for comparisons between GLUT4-null and wild-type mice in each experimental condition. GLUT = glucose transporter.
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