Knocking Out Answers to Diabetes: Role of SSTR5

Diabetes affects more than 15 million Americans with enormous economic impact on our healthcare system [1]. The biological basis for diabetes, therefore, is an area of intense basic science and translational research. Critical to making progress in diabetes research and developing new treatments is understanding the complexities of regulated insulin secretion and pancreatic islet health. Somatostatin, a potent inhibitory neuropeptide, has long been known to inhibit insulin secretion, but its exact role in islet physiology and diabetes is not completely understood [2]. Somatostatin (SST) hormone activity is mediated through SST-14 and SST-28 isoforms that differentially bind to the five different SST receptor subtypes (SSTR1-5) [3]. Human islet -cells express SSTR1 and SSTR5. Consequently, SST binding to either of these receptors could affect insulin secretion. On the other hand, islet -cells express SSTR2 and -cells express SSTR5—thus illustrating the specific molecular signature each islet cell type has for a unique response to SST. Since islets have a mixed cell population ( , , , and others) arranged in an organized configuration (mantle and core) with an intraislet portal circulation, SST could regulate insulin secretion either by a direct -cell secreted SST paracrine effect or by a systemic SST effect, or perhaps a complex interplay of both routes. Although it is known that SST inhibits insulin secretion, it is unknown to what extent each of the SSTR receptor subtype contributes to the regulation of insulin secretion and the complex interplay of islet cell types and the systemic response. For more than a decade Brunicardi et al. have studied the role of somatostatin and SSTRs in regulation of insulin secretion to further our understanding of islet physiology and diabetes. Initial studies used SST analogues and transfected SSTR gene expression constructs