HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Simões, M. V. Articles by Schwaiger, M. Search for Related Content PubMed PubMed Citation Articles by Simões, M. V. Articles by Schwaiger, M.

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

Manuscript received July 20, 2003; revised manuscript received November 27, 2003, accepted December 9, 2003.

^* Reprint requests and correspondence: Dr. Marcus V. Simões, Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675 Munich, Germany.
msimoes{at}fmrp.usp.br

OBJECTIVES: We sought to evaluate the time course of insulin-stimulated myocardial glucose uptake (MGU) in mice that had undergone ablation of glucose transporter-4 (GLUT4).

BACKGROUND: The relative importance of GLUT4, the most abundant insulin-responsive glucose transporter, to modulate myocardial glucose metabolism is not well defined.

METHODS: Myocardial glucose uptake was assessed at various time points after glucose (1 mg/g) and insulin (8 mU/g) injection in GLUT4-null (G4N) (n = 48) and wild-type (WT) (n = 48) mice with ¹⁸F-2-deoxy-2-fluoro-D-glucose (FDG) using in vivo positron emission tomography (PET), in vitro gamma-counter biodistribution, and isolated, perfused hearts.

RESULTS: Baseline assessment with PET imaging showed comparable MGU in G4N (0.66 ± 0.12) and WT (0.67 ± 0.11, p = 0.70) mice. Early after insulin injection, WT mice demonstrated a 3.5-fold increase in MGU (2.45 ± 0.45, p = 0.03), whereas G4N mice presented no increase (1.11 ± 0.24, p = 0.28). At 60 min, MGU was comparable in G4N (3.19 ± 0.60) and WT (2.66 ± 0.47, p = 0.28) mice. In vitro gamma-counter biodistribution evaluation confirmed in G4N mice a lack of MGU increase early after insulin, but a slow response over 120 min. The isolated, perfused hearts of G4N mice during short-term (15 min) insulin stimulation displayed no increase in MGU (0.08 ± 0.01 ml/g/min), whereas WT mice presented a threefold increase (0.22 ± 0.01 ml/g/min, p < 0.01). With long-term (60 min) insulin stimulation, similar MGU was found in G4N (0.31 ± 0.02 ml/g/min) and WT (0.33 ± 0.04 ml/g per min, p = 0.04) mice.

CONCLUSIONS: The G4N mice displayed an increase of MGU in response to insulin similar to that of controls, but with a markedly delayed time response. Our findings underscore the important role of GLUT4 in the rapid adaptive response of myocardial glucose metabolism.

Abbreviations and Acronyms   2-DG = 2-deoxyglycose   FDG = 18F-2-deoxy-2-fluoro-D-glucose   GLUT = glucose transporter   G4N = GLUT4-null mice   MGU = myocardial glucose uptake   PET = positron emission tomography   SUV = standard uptake value   WT = wild-type mice

This article has been cited by other articles:

				M. C. Kreissl, H.-M. Wu, D. B. Stout, W. Ladno, T. H. Schindler, X. Zhang, J. O. Prior, M. L. Prins, A. F. Chatziioannou, S.-C. Huang, et al. Noninvasive Measurement of Cardiovascular Function in Mice with High-Temporal-Resolution Small-Animal PET J. Nucl. Med., June 1, 2006; 47(6): 974 - 980. [Abstract] [Full Text] [PDF]