Expression of fatty acid binding proteins 3 and 5 genes in rat pancreatic islets and INS-1E cells: regulation by fatty acids and glucose.

Fatty acids binding proteins (FABPs) are involved in uptake, binding, transport and metabolism of fatty acids (FAs). Although FAs are known to stimulate insulin secretion from pancreatic islets when transiently elevated, while contributing to islet loss of function, lipotoxicity and apoptosis when chronically elevated, almost nothing is known regarding the FABPs in this tissue. The present study aimed at exploring the expression pattern and regulation of FABPs in rat islets and the insulin-secreting INS-1E cells. Rat islets and INS-1E cells expressed the heart/muscle type (FABP3) and the epidermal type (FABP5) genes. Different FAs significantly enhanced the expression of both FABPs. High glucose concentration induced a similar elevation of both FABP mRNA levels, and similarly to its effect on insulin 1 mRNA. Addition of oleic or palmitic acids to glucose did not render a further effect. FABP3 gene expression increased in response to PPARα agonist, while FABP5 increased in response to PPARα and PPARγ agonists, and decreased in response to a PPARβ agonist. Beta-oxidation of FAs is required for the gene expression of both FABP genes in INS-1E cells. Inhibition of CPT-1 by etomoxir inhibited the oleic acid-induced FABP 3 and 5 gene expression, while activation of AMPK by metformin amplified the oleic-induced expression of both FABPs. FABP3 and 5 gene transcription required de novo protein synthesis, since inhibition by cycloheximide significantly decreased both FABP mRNAs. These data show a complex interrelationship between glucose and FAs in the control of FABP gene expression and that FABP3 and 5 may play a role in insulin secretion.

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