Figure 5.

Proposed model of regulation of glucagon secretion. α-Cells are activated by a lowering of glucose concentration. Under constant conditions, glucagon secretion wanes because voltage-gated channels inactivate and ionotropic glutamate receptors desensitize (red cloud). When glucose levels increase, β-cells secrete insulin and other paracrine factors that inhibit α-cells, among others, by hyperpolarizing the cell via GABA_A receptors. This allows voltage-gated ion channel and ionotropic glutamate receptors to recover from inactivation and desensitization (green star). In type 1 diabetes, α-cells are locked in the refractory state shown on the right because they cannot be reset by β-cell input. GluR_2/3, iGluRs of the AMPA type composed by GluR₂ and GluR₃ subunits; VGCC, voltage-gated Ca²⁺ channels.