Fig. 10. Role of kinesin-mediated vesicle translocation in glucose-stimulated secretion. Typical biphasic insulin secretion from pancreatic islet ß-cells when glucose concentration is elevated to 16 mM (upper panel) and the corresponding glucose-stimulated vesicle movements (lower panel) are shown. (1) At sub-stimulatory [glucose], a small proportion (5% of total) (Rorsman et al., 2000) of granules is docked and immediately available for release (releasable pool). However, most of the granules are situated some distance from the plasma membrane in a `reserve pool' and need to be chemically modified or physically translocated to release sites. (2) Shortly after elevation of [glucose], granules that are already docked undergo exocytosis and transient stimulation of insulin secretion is observed. (3) Kinesin-dependent vesicle recruitment. Note that the nadir in the rate of secretion between end of exocytosis of vesicles in the releaseable pool (2), and the activation of kinesin-dependent vesicle recruitment (3) is postulated to be longer in islets than cell lines, where the two phases of secretion are not readily distinguished. (4) ATP-dependent mobilisation of granules from the reserve pool via kinesin-mediated transport. This stage represents the sustained release of insulin. (5) KHC^mut blocks the transport of granules from the reverse pool by irreversibly binding to microtubules (Nakata and Hirokawa, 1995; Krylyshkina et al., 2002) and inhibits the second phase of insulin release. KHC, kinesin heavy chain; KHC^mut, motor domain of kinesin heavy chain containing a T93N point mutation; KLC, kinesin light chain; MT, microtubule.