Amino acid-induced gene expression profiling in clonal β-cell line INS-1E cells

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.