Ustione Alessandro, Piston David W, Harris Paul E
Department of Molecular Physiology and Biophysics, Vanderbilt University, 702 Light Hall, Nashville, Tennessee 37232-0615, USA.
Mol Endocrinol. 2013 Aug;27(8):1198-207. doi: 10.1210/me.2013-1083. Epub 2013 Jun 6.
Exogenous dopamine inhibits insulin secretion from pancreatic β-cells, but the lack of dopaminergic neurons in pancreatic islets has led to controversy regarding the importance of this effect. Recent data, however, suggest a plausible physiologic role for dopamine in the regulation of insulin secretion. We review the literature underlying our current understanding of dopaminergic signaling that can down-regulate glucose-stimulated insulin secretion from pancreatic islets. In this negative feedback loop, dopamine is synthesized in the β-cells from circulating L-dopa, serves as an autocrine signal that is cosecreted with insulin, and causes a tonic inhibition on glucose-stimulated insulin secretion. On the whole animal scale, L-dopa is produced by cells in the gastrointestinal tract, and its concentration in the blood plasma increases following a mixed meal. By reviewing the outcome of certain types of bariatric surgery that result in rapid amelioration of glucose tolerance, we hypothesize that dopamine serves as an "antiincretin" signal that counterbalances the stimulatory effect of glucagon-like peptide 1.
外源性多巴胺可抑制胰腺β细胞分泌胰岛素，但胰岛中缺乏多巴胺能神经元，这使得这种作用的重要性存在争议。然而，最近的数据表明多巴胺在胰岛素分泌调节中可能具有合理的生理作用。我们回顾了相关文献，这些文献是我们目前对多巴胺能信号传导理解的基础，多巴胺能信号传导可下调胰岛对葡萄糖刺激的胰岛素分泌。在这个负反馈回路中，多巴胺由循环中的左旋多巴在β细胞中合成，作为与胰岛素共同分泌的自分泌信号，并对葡萄糖刺激的胰岛素分泌产生持续性抑制。在整个动物层面，左旋多巴由胃肠道细胞产生，混合餐后其血浆浓度会升高。通过回顾某些类型的减肥手术的结果，这些手术可迅速改善糖耐量，我们推测多巴胺作为一种“抗肠促胰岛素”信号，可抵消胰高血糖素样肽1的刺激作用。
