In pancreatic beta cells, insulin secretion is trigged by calcium and greatly amplified by cAMP/protein kinase A (PKA), protein kinase C (PKC) and some tyrosine kinases.Numerous studies showed the interaction of calcium signaling and cAMP signaling in beta cells and their function in insulin secretion.For example, glucose induces a biphasic insulin release with calcium increase, followed by cAMP generation, and glucagon-like peptide 1 (GLP-1) enhances glucose-induced insulin secretion through elevated cAMP levels.However, the relationships between calcium and other key regulators of insulin release are largely unkown.Protein tyrosine phosphatase (PTP1B) is expressed widely including the insulin targeted tissues and insulin-secreting cells.It is localized to the cytoplasmic face of the endoplasmic reticulum calcium stores.Here we report the roles of PTPlB on calcium signaling and insulin secretion in pancreatic beta cells.