Figure 4.

Two hypothesized models of synergism forβ-cell insulin secretion. (a) According to the cell heterogeneity model, unique populations ofβ cells exist that do not express all three incretin/glucagon receptors. In this model, the triagonist increases insulin secretion compared with a monoagonist by engaging multipleβ-cell subgroups to stimulate insulin secretion. (b) In the intracellular amplification model,β cells express all incretin/glucagon receptors, and the synergistic activity of the triagonist compared with the monoagonist is based on the crosstalk of downstream signaling cascades within an individualβ cell.