胰腺可以合成多巴胺（DA），而DA可以调节血糖和胰岛素分泌，但DA来自胰腺外分泌部还是内分泌部、它如何调节胰岛素分泌均不清楚。有报道合成DA的限速酶分布在胰腺腺泡、而DA转运体在胰岛β细胞。我们发现胰液中存在高浓度左旋多巴（L-DOPA），DA受体大量分布在胰岛，其中D1受体定位在β细胞。我们推测腺泡细胞利用酪氨酸合成L-DOPA；L-DOPA经胰腺导管到达胰岛β细胞合成DA；DA通过自分泌作用于D1受体调节胰岛素分泌。本项目将采用免疫荧光、选择性胰岛β细胞破坏、腺泡/胰岛细胞培养与共培养、流式细胞、RNA干扰/基因敲除等深入研究胰腺内/外分泌之间联系的形态结构；胰液中L-DOPA的来源；明确胰岛合成DA的前体；以及胰岛β细胞自分泌DA通过D1受体调节胰岛素分泌。本研究有助于揭示胰腺DA的合成过程及其通过D1调节胰岛素分泌的机制，有望为探索糖尿病诊治的药物靶点提供可靠的理论与实验依据。

Dopamine (DA) synthesized in pancreas can regulate insulin secretion and blood glucose level. But which part of pancreas the DA comes from, exocrine or endocrine, and how it regulates insulin secretion remains unclear. It has been reported that the rate-limiting enzyme for DA synthesis is distributed in the pancreatic acinar, while the DA transporter is located in the islet β cells. We have detected a high concentration of levodopa (L-DOPA) in pancreatic juice and wide distribution of DA receptors in pancreatic islets, among which the D1 receptors are only localized in β cells. We hypothesize that acinar cells may uptake tyrosine for L-DOPA synthesis; islets cells synthesize DA by taking the L-DOPA from acinar cells, not tyrosine; and by binding with D1 receptors on the islet β cells the DA stimulates insulin secretion in an autocrine manner. The present study aims to investigate the structural communication between endocrine and exocrine pancreas; the synthesis of DA in islets, the manner of DA released by islet β cell, and the signaling pathway underlying the DA modulating insulin secretion by means of immunofluorescence, selective destruction of pancreatic β cells, acinar/islet cell culture and co-culture, flow cytometry, RNA interference/gene knockdown and radioactive detection etc. The present study may reveal the synthesis and autocrine of DA in pancreas and the mechanisms underlying the regulation of pancreatic DA on insulin secretion. In addition, it might also provide some theoretical and experimental evidence for searching drug target of diabetes' diagnosis and treatment.