Delayed response of insulin-stimulated fluorine-18 deoxyglucose uptake in glucose transporter-4-null mice hearts

Marcus V. Simões, Silvia Egert, Sibylle Ziegler, Masao Miyagawa, Sybille Reder, Terry Lehner, Ngoc Nguyen, Maureen J. Charron, Markus Schwaiger

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1690-1697
Number of pages8
JournalJournal of the American College of Cardiology
Volume43
Issue number9
DOIs
StatePublished - May 5 2004

Fingerprint

Facilitative Glucose Transport Proteins
Fluorine
Deoxyglucose
Insulin
Glucose
Positron-Emission Tomography
Glucose Transporter Type 4
Injections
Fluorodeoxyglucose F18

Keywords

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

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Delayed response of insulin-stimulated fluorine-18 deoxyglucose uptake in glucose transporter-4-null mice hearts. / Simões, Marcus V.; Egert, Silvia; Ziegler, Sibylle; Miyagawa, Masao; Reder, Sybille; Lehner, Terry; Nguyen, Ngoc; Charron, Maureen J.; Schwaiger, Markus.

In: Journal of the American College of Cardiology, Vol. 43, No. 9, 05.05.2004, p. 1690-1697.

Research output: Contribution to journalArticle

Simões, Marcus V. ; Egert, Silvia ; Ziegler, Sibylle ; Miyagawa, Masao ; Reder, Sybille ; Lehner, Terry ; Nguyen, Ngoc ; Charron, Maureen J. ; Schwaiger, Markus. / Delayed response of insulin-stimulated fluorine-18 deoxyglucose uptake in glucose transporter-4-null mice hearts. In: Journal of the American College of Cardiology. 2004 ; Vol. 43, No. 9. pp. 1690-1697.
@article{66f59a1e780e47939831a33beb5bf4f5,
title = "Delayed response of insulin-stimulated fluorine-18 deoxyglucose uptake in glucose transporter-4-null mice hearts",
abstract = "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.",
keywords = "2-deoxyglycose, 2-DG, F-2-deoxy-2-fluoro-D-glucose, FDG, G4N, glucose transporter, GLUT, GLUT4-null mice, MGU, myocardial glucose uptake, PET, positron emission tomography, standard uptake value, SUV, wild-type mice, WT",
author = "Sim{\~o}es, {Marcus V.} and Silvia Egert and Sibylle Ziegler and Masao Miyagawa and Sybille Reder and Terry Lehner and Ngoc Nguyen and Charron, {Maureen J.} and Markus Schwaiger",
year = "2004",
month = "5",
day = "5",
doi = "10.1016/j.jacc.2003.12.038",
language = "English (US)",
volume = "43",
pages = "1690--1697",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "9",

}

TY - JOUR

T1 - Delayed response of insulin-stimulated fluorine-18 deoxyglucose uptake in glucose transporter-4-null mice hearts

AU - Simões, Marcus V.

AU - Egert, Silvia

AU - Ziegler, Sibylle

AU - Miyagawa, Masao

AU - Reder, Sybille

AU - Lehner, Terry

AU - Nguyen, Ngoc

AU - Charron, Maureen J.

AU - Schwaiger, Markus

PY - 2004/5/5

Y1 - 2004/5/5

N2 - 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.

AB - 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.

KW - 2-deoxyglycose

KW - 2-DG

KW - F-2-deoxy-2-fluoro-D-glucose

KW - FDG

KW - G4N

KW - glucose transporter

KW - GLUT

KW - GLUT4-null mice

KW - MGU

KW - myocardial glucose uptake

KW - PET

KW - positron emission tomography

KW - standard uptake value

KW - SUV

KW - wild-type mice

KW - WT

UR - http://www.scopus.com/inward/record.url?scp=18344412288&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18344412288&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2003.12.038

DO - 10.1016/j.jacc.2003.12.038

M3 - Article

C2 - 15120832

AN - SCOPUS:18344412288

VL - 43

SP - 1690

EP - 1697

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 9

ER -