Fusion pore dynamics and insulin granule exocytosis in the pancreatic islet.

Insulin secretion from intact mouse pancreatic islets was investigated with two-photon excitation imaging. Insulin granule exocytosis occurred mainly toward the interstitial space, away from blood vessels. The fusion pore was unusually stable with a lifetime of 1.8 seconds. Opening of the 1.4-nanometer-diameter pore was preceded by unrestricted lateral diffusion of lipids along the inner wall of the pore, supporting the idea that this structure is composed of membrane lipids. When the pore dilated to 12 nanometers, the granules rapidly flattened and discharged their contents. Thus, our methodology reveals fusion pore dynamics in intact tissues at nanometer resolution.