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Amino acid‐induced gene expression profiling in clonal β‐cell line INS‐1E cells
Author(s) -
Liu Zhenping,
Luo Yonglun,
Jeppesen Per Bendix,
Gregersen Søren,
Hermansen Kjeld
Publication year - 2011
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1153
Subject(s) - biology , gene expression , gene expression profiling , cell , microbiology and biotechnology , gene , biochemistry
Background There is abundant evidence that glucotoxicity and lipotoxicity contribute to impaired β‐cell function in type 2 diabetes. Interestingly, amino acid (AA) derangement is also a characteristic part of the diabetic state. The acute effects of AA on pancreatic β‐cell function have been widely explored; however, to our knowledge, the chronic effects of AA, e.g. proline (Pro), homocysteine (Hcy), and leucine (Leu), on pancreatic β‐cell function and integrity have not yet been studied. We aimed to investigate global alterations in β‐cell gene expression after long‐term exposure of clonal INS‐1E cells to elevated level of specific AA in vitro . Methods Global gene expression profiling was performed to characterize genes differently modified by Pro, Hcy, and Leu, respectively, in INS‐1E cells. Results Gene expression profiling revealed significant changes in INS‐1E cell mRNAs involved in the control of several aspects of β‐cell function, e.g. epigenetic regulation of gene expression, metabolism, innate and adaptive immune responses, cellular signalling, protein synthesis, apoptosis, and cellular stress response. After 72 h, INS‐1E cells were differentially regulated (≥1.5‐ or ≤ −1.5‐fold) by Pro (295 transcripts), Hcy (301 transcripts), and Leu (701 transcripts). It appears that Hcy effects changes opposite to those induced by Leu and/or Pro. Conclusions AA appears to participate in and to influence many physiological processes including those involved in cholesterol metabolism, immune responses, and oxidative phosphorylation. Whether such events promote the β‐cell dysfunction and the β‐cell failure in diabetes remains to be elucidated. Our data strongly indicate that AA elevation may take part in the progressive development of type 2 diabetes. Copyright © 2011 John Wiley & Sons, Ltd.