Regulation of the type III InsP3 receptor and its role in β cell function

Abstract.

The type III inositol 1,4,5-trisphosphate receptor (InsP₃R) is an important intracellular calcium (Ca²⁺) release channel in the pancreatic β cell. Pancreatic β cells secrete insulin following a characteristic change in membrane potential that leads to an increase in cytoplasmic Ca²⁺. Both extracellular Ca²⁺ and Ca²⁺ mobilized from InsP₃-sensitive stores contribute to this increase. RIN-m5F cells, an insulin-secreting β cell line, preferentially express the type III InsP₃R . These cells have been useful in determining the regulatory properties of the type III InsP₃R and the role of this isoform in an intact cell. The type III InsP₃R is ideal for signal initiation because high cytoplasmic Ca²⁺ does not inhibit its activity . Altered insulin secretion, the result of changes in Ca²⁺ handling by the β cell, has significant clinical consequences.