| Abstract | Insulin secretion from pancreatic beta-cells shares many features with neural transmitter release. For example, both are triggered by calcium entry through voltage-dependent calcium channels. Beta-cells also have unique features, particularly the dependence of calcium elevation on glucose metabolism and the division of release into two phases, an intense but transient first phase and a sustained second phase. Loss of first phase is an early predictor of type 2 diabetes. Grodsky and colleagues proposed forty years ago that the first phase was mediated by a readily releasable pool of vesicles docked at the plasma membrane whereas the second phase was mediated by the slow delivery of new vesicles from a reserve pool. This model has stood up well over time but needs modification. Recent models have distinguished the calcium-raising and vesicle mobilizing effects of the glucose stimulus. We will discuss a new model which goes a step further to show that the second phase may be carried mainly by a newly discovered pool of vesicle with enhanced calcium sensitivity. These vesicles may coincide with another, more controversial, pool of vesicles claimed to fuse rapidly after arrival at the plasma membrane, avoiding a prolonged period of being docked and ready. |
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