Integrative function of adrenaline receptors for glucagon-like peptide-1 exocytosis in enteroendocrine L cell line GLUTag

Adrenaline reacts with three types of adrenergic receptors, alpha 1, alpha 2 and beta-adrenergic receptors (ARs), inducing many physiological events including exocytosis. Although adrenaline has been shown to induce glucagon-like peptide-1 (GLP-1) secretion from intestinal L cells, the precise molecular mechanism by which adrenaline regulates GLP-1 secretion remains unknown. Here we show by live cell imaging that all types of adrenergic receptors are stimulated by adrenaline in enteroendocrine L cell line GLUTag cells and are involved in GLP-1 exocytosis. We performed RT-PCR analysis and found that alpha 1B-, alpha 2A-, alpha 2B-, and beta 1-ARs were expressed in GLUTag cells. Application of adrenaline induced a significant increase of intracellular Ca2+ and CAMP concentration ([Ca2+]; and [cAMP](i), respectively), and GLP-1 exocytosis in GLUTag cells. Blockade of alpha 1-AR inhibited adrenaline-induced [Ca2+](i) increase and exocytosis but not [cAMP](i) increase, while blockade of beta 1-AR inhibited adrenaline-induced [cAMP]; increase and exocytosis but not [Ca2+]; increase. Furthermore, overexpression of alpha 2A-AR suppressed the adrenaline-induced [cAMP](i) increase and exocytosis. These results suggest that the fine-turning of GLP-1 secretion from enteroendocrine L cells is established by the balance between alpha 1-, alpha 2-, and beta-ARs activation. (C) 2015 Elsevier Inc. All rights reserved.