Insulin Stimulates Long-Chain Fatty Acid Utilization by Rat Cardiac Myocytes Through Cellular Redistribution of FAT/CD36
Abstract
The existence of an intracellular pool of fatty acid translocase (FAT/CD36), an 88-kDa membrane transporter for long-chain fatty acids (FAs), and the ability of insulin to induce translocation events prompted us to investigate the direct effects of insulin on cellular uptake of FA by the heart. Insulin (0.1 nmol/l and higher) increased FA uptake by isolated rat cardiac myocytes by 1.5-fold. This insulin-induced increase in FA uptake was completely blocked by phloretin, sulfo-N-succinimidylpalmitate (SSP), and wortmannin, indicating the involvement of FAT/CD36 and the dependence on phosphatidylinositol-3 (PI-3) kinase activation. Subcellular fractionation of insulin-stimulated cardiac myocytes demonstrated a 1.5-fold increase in sarcolemmal FAT/CD36 and a 62% decrease in intracellular FAT/CD36 with parallel changes in subcellular distribution of GLUT4. Induction of cellular contractions upon electrostimulation at 4 Hz enhanced cellular FA uptake 1.6-fold, independent of PI-3 kinase. The addition of insulin to 4 Hz-stimulated cells further stimulated FA uptake to 2.3-fold, indicating that there are at least two functionally independent intracellular FAT/CD36 pools, one recruited by insulin and the other mobilized by contractions. In conclusion, we have demonstrated a novel role of insulin in cardiac FA utilization. Malfunctioning of insulin-induced FAT/CD36 translocation may be involved in the development of type 2 diabetic cardiomyopathies.
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Increased plasmalemma skeletal muscle CD36 is associated with increased FFA uptake and insulin resistance in animal models and obese and diabetic human subjects.
“The potential importance of CD36 in regulating insulin sensitivity is supported by studies conducted in animal models and in obese and diabetic human subjects that found increased plasmalemma skeletal muscle CD36 was associated with increased FFA uptake and insulin resistance (25,30,31)”
From Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity (2009) · cites this paper as [31]
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References 39 · Cited by 260
- Authors
- Luiken, J. J. F. P., Koonen, D. P. Y., Willems, J., Zorzano, A., Becker, C., Fischer, Y., Tandon, N. N., van der Vusse, G. J., Bonen, A., & Glatz, J. F. C.
- Affiliations
- Maastricht University (NL)
- Department de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
- RWTH Aachen University (DE)
- Otsuka (United States) (US)
- Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
- University of Waterloo (CA)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2002-10-01
- Volume
- 51
- Issue
- 10
- Pages
- 3113-3119
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2158592541
- Cited by
- 260
- References
- 39
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 7 · 2023: 6 · 2022: 5 · 2021: 15 · 2020: 8 · 2019: 6 · 2018: 5 · 2017: 11 · 2016: 10 · 2015: 10 · 2014: 11 · 2013: 5 · 2012: 22
- FWCI
- 8.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- insulin, long-chain fatty acid uptake, cardiomyocytes, fatty acid utilization, PI3-kinase, GLUT4, sarcolemma, phloretin, wortmannin, cardiac contraction, subcellular redistribution
- MeSH terms
- Wortmannin, Androstadienes, Animals, Biological Transport, Deoxyglucose, Diabetes Mellitus, Type 2, Electric Stimulation, Enzyme Inhibitors, Hypoglycemic Agents, Insulin, Insulin Resistance, Male, Membrane Glycoproteins, Myocardial Contraction, Myocardium, Palmitates, Phloretin, Rats, Inbred Lew, Succinimides, Muscle Fibers, Skeletal, CD36 Antigens, Transport Vesicles, Organic Anion Transporters, Rats
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