Dopamine Synthesis and D3 Receptor Activation in Pancreatic beta-Cells Regulates Insulin Secretion and Intracellular [Ca2+] Oscillations

作者：Ustione Alessandro; Piston David W^*

来源：Molecular Endocrinology, 2012, 26(11): 1928-1940.

DOI：10.1210/me.2012-1226

Pancreatic islets are critical for glucose homeostasis via the regulated secretion of insulin and other hormones. We propose a novel mechanism that regulates insulin secretion from beta-cells within mouse pancreatic islets: a dopaminergic negative feedback acting on insulin secretion. We show that islets are a site of dopamine synthesis and accumulation outside the central nervous system. We show that both dopamine and its precursor L-dopa inhibit glucose-stimulated insulin secretion, and this inhibition correlates with a reduction in frequency of the intracellular [Ca2+] oscillations. We further show that the effects of dopamine are abolished by a specific antagonist of the dopamine receptor D3. Because the dopamine transporter and dopamine receptors are expressed in the islets, we propose that cosecretion of dopamine with insulin activates receptors on the beta-cell surface. D3 receptor activation results in changes in intracellular [Ca2+] dynamics, which, in turn, lead to lowered insulin secretion. Because blocking dopaminergic negative feedback increases insulin secretion, expanding the knowledge of this pathway in beta-cells might offer a potential new target for the treatment of type 2 diabetes. (Molecular Endocrinology 26: 1928-1940, 2012)

• 出版日期2012-11