Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104-4318, USA.
Mol Cell Endocrinol. 2010 Aug 30;325(1-2):36-45. doi: 10.1016/j.mce.2010.05.008.
The novel islet-specific protein PANcreatic DERived Factor (PANDER; FAM3B) has been extensively characterized with respect to the beta-cell, and these studies suggest a potential function for PANDER in the regulation of glucose homeostasis. Little is known regarding PANDER in pancreatic -cells, which are critically involved in maintaining euglycemia. Here we present the first report elucidating the expression and regulation of PANDER within the alpha-cell. Pander mRNA and protein are detected in alpha-cells, with primary localization to a glucagon-negative granular cytosolic compartment. PANDER secretion from alpha-cells is nutritionally and hormonally regulated by l-arginine and insulin, demonstrating similarities and differences with glucagon. Signaling via the insulin receptor (IR) through the PI3K and Akt/PKB node is required for insulin-stimulated PANDER release. The separate localization of PANDER and glucagon is consistent with their differential regulation, and the effect of insulin suggests a paracrine/endocrine effect on PANDER release. This provides further insight into the potential glucose-regulatory role of PANDER.
新型胰岛特异性蛋白 PANcreatic DERived Factor（PANDER；FAM3B）在β细胞方面的特征已得到广泛研究，这些研究表明 PANDER 在调节葡萄糖稳态方面具有潜在功能。然而，关于在胰腺α细胞中发挥关键作用的 PANDER 知之甚少，α细胞在维持血糖平衡中起着至关重要的作用。本文首次报道了阐明 PANDER 在α细胞中的表达和调节。在α细胞中检测到 Pander mRNA 和蛋白，主要定位于一种胰高血糖素阴性的颗粒胞质区室。α细胞中 PANDER 的分泌受到 l-精氨酸和胰岛素的营养和激素调节，这与胰高血糖素具有相似性和差异性。通过胰岛素受体（IR）通过 PI3K 和 Akt/PKB 节点的信号转导对于胰岛素刺激的 PANDER 释放是必需的。PANDER 和胰高血糖素的分离定位与其差异调节一致，而胰岛素的作用表明对 PANDER 释放具有旁分泌/内分泌作用。这为 PANDER 的潜在葡萄糖调节作用提供了进一步的见解。
