Transmembrane Emp24 Protein Transport Domain 6 is Selectively Expressed in Pancreatic Islets and Implicated in Insulin Secretion and Diabetes

Objectives: The objective of the study was to identify pancreatic islet-selective gene(s) that may play a functional role in islet biology and diabetes development. Methods: Through bioinformatics, we identified and cloned a pancreas-enriched complementary DNA encoding transmembrane emp24 protein transport domain 6 (TMED6) and examined its mRNA and protein expression in tissues and islet cell lines by Northern analysis and immunofluorescence histochemistry. We also studied the role of TMED6 in insulin secretion using a knockdown approach and its gene expression changes during the development of diabetes in Goto-Kakizaki rats. Results: TMED6 is selectively expressed in pancreatic islets and belongs to the EMP24_GP25L superfamily, which is known to be involved in protein trafficking and secretion. Northern analysis revealed that TMED6 mRNA is highly and selectively expressed in pancreas. Immunofluorescence histochemistry of mouse pancreas showed that TMED6 expression is restricted to pancreatic islets with higher levels in alpha cells than beta cells. Knockdown of TMED6 gene expression in Min6 beta cells decreased insulin secretion. Moreover, TMED6 gene expression was significantly lower in diabetic Goto-Kakizaki rats. Conclusions: TMED6 may play a functional role in islet biology, particularly in hormone production or secretion, and its dysregulation may be implicated in the development of diabetes.