The classic or "consensus" model of glucose-induced insulin secretion focuses on K_ATP channels of the b-cell membrane.Their closure by nucleotides, produced during glucose metabolism, certainlypermits depolarization with stimulation of calcium influx, which leads to the indispensable increase in cytosolic [Ca²⁺]_c to trigger exocytosis of insulin granules. However, the model is incomplete. Experiments using b-cells lacking K_ATP channels have shown that as yet unidentified biophysical targets, other than K_ATP channels, are under metabolic influence and can control the triggering Ca²⁺ signal. In addition, independently of its action on K_ATP channels, glucose also turns on a metabolicamplifying pathway that augments insulin secretion without further increasing triggering [Ca²⁺]_c. Metabolic amplification is distinct from the neurohormonal amplifying pathways set in operation by ligand-activated membrane receptors, which transduce the parasympathetic and incretin-mediated potentiation of insulin secretion during meals. Metabolic amplification, originally disclosed during pharmacological clamping of b-cell [Ca²⁺]_c at an elevated level, is also operative during physiological fluctuations of [Ca²⁺]_c. Contrary to widely held views, it augments both first and second phases of glucose-induced insulin secretion and does not involve insulin granule recruitment by the cytoskeleton of microtubules and microfilaments. It could correspond to acceleration of the priming process conferring release competence to secretory granules. Metabolic amplification is quantitatively important, contributing to about 50% of glucose-induced insulin secretion, but is only second in the hierarchy. Thus, it remains ineffective as long as the triggering Ca²⁺ signal is not produced by the K_ATP channel-dependent pathway.