On the other hand, we were unable to detect any impairment in glucose or depolarization-induced insulin secretion as assessed ex vivo in isolated islets (Fig. 8). Indeed, in islets isolated from animals maintained on either RC or HFD, we observed a tendency in male βVps13cKO mice toward enhanced insulin secretion in response to either high glucose or KCl and in female βVps13cKO in response to high glucose. By contrast, stimulated insulin secretion in response to KCl tended not to change in βVps13cKO vs. control islets from females fed RC or HFD. We are therefore unable at the present time to assign the changes in β-cell function and glucose homeostasis observed in vivo unambiguously to alterations in islet responses measureable in vitro. We would stress, however, that the mechanisms responsible for the stimulation of insulin secretion by elevated glucose in vivo, which are likely to be modulated by a multitude of humoral (e.g., circulating fatty acids, incretins, adipokines, etc.), neuronal (56), and other inputs into the islet, are unlikely to match perfectly those tested in vitro.