Visualizing Insulin Granule Secretion

To secrete insulin is what beta cells are made for. To do so, beta cells store insulin in granules that are released upon stimulation. This is a highly controlled process. Many signals such as blood sugar levels and hormones stimulate the beta cell. In response, beta cells change cytoplasmic Ca2+ levels and cAMP levels, to name just two of the many intracellular responses that can be elicited. Despite this diversity in intracellular signaling, the beta cell has only one major output: insulin secretion through granule fusion. We developed a technique to visualize this event in real time in intact human islets. A striking feature in our recordings is that these granule fusion events are very discrete, extremely synchronized, and rhythmic. The image sequence shows a beta cell within a human islet at four different time points. The beta cell membrane is labeled in red. Single insulin granules (green) can be seen fusing with the membrane at time points 2 and 3. The trace on the right shows the change in green fluorescence that occurs in the regions delineated in the first image.