Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 303, Issue 7, Pages E899-E907Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00116.2012
Keywords
carrier-mediated transport; cluster of differentiation 36; fatty acid uptake; GLUTag; monounsaturated fatty acid
Categories
Funding
- Canadian Institutes of Health Research
- Banting and Best Diabetes Centre (BBDC), University of Toronto
- Endocrine Society
- Department of Physiology, University of Toronto
- Canada Research Chairs program
- Canadian Diabetes Association [2973]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIH R01-AR-049269]
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Poreba MA, Dong CX, Li SK, Stahl A, Miner JH, Brubaker PL. Role of fatty acid transport protein 4 in oleic acid-induced glucagon-like peptide-1 secretion from murine intestinal L cells. Am J Physiol Endocrinol Metab 303: E899-E907, 2012. First published August 7, 2012; doi: 10.1152/ajpendo.00116.2012.-The antidiabetic intestinal L cell hormone glucagon-like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion and inhibits gastric emptying. GLP-1 secretion is stimulated by luminal oleic acid (OA), which crosses the cell membrane by an unknown mechanism. We hypothesized that L cell fatty acid transport proteins (FATPs) are essential for OA-induced GLP-1 release. Therefore, the murine GLUTag L cell model was used for immunoblotting, [H-3]OA uptake assay, and GLP-1 secretion assay as determined by radioimmunoassay following treatment with OA +/- phloretin, sulfo-N-succinimidyl oleate, or siRNA against FATP4. FATP4(-/-) and cluster-of-differentiation 36 (CD36)(-/-) mice received intraileal OA, and plasma GLP-1 was measured by sandwich immunoassay. GLUTag cells were found to express CD36, FATP1, FATP3, and FATP4. The cells demonstrated specific H-3[OA] uptake that was dose-dependently inhibited by 500 and 1,000 mu M unlabeled OA (P < 0.001). Cell viability was not altered by treatment with OA. Phloretin and sulfo-N-succinimidyl oleate, inhibitors of protein-mediated transport and CD36, respectively, also decreased [H-3]OA uptake, as did knockdown of FATP4 by siRNA transfection (P < 0.05-0.001). OA dose-dependently increased GLP-1 secretion at 500 and 1,000 mu M (P < 0.001), whereas phloretin, sulfo-N-succinimidyl oleate, and FATP4 knockdown decreased this response (P < 0.05-0.01). FATP4(-/-) mice displayed lower plasma GLP-1 at 60 min in response to intraileal OA (P < 0.05), whereas, unexpectedly, CD36(-/-) mice displayed higher basal GLP-1 levels (P < 0.01) but a normal response to intraileal OA. Together, these findings demonstrate a key role for FATP4 in OA-induced GLP-1 secretion from the murine L cell in vitro and in vivo, whereas the precise role of CD36 remains unclear.
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