Fig. 3.

Model of the mechanism underlying excessive glucagon secretion induced by high glucose. Left: Insulin signaling suppresses glucagon secretion by reducing the sensitivity of ${\text{K}}_{\text{ATP}}^{+}$ channels via PI3K, or by recruiting the GABA-A receptor to the cellular membrane via Akt. Right: Insulin signaling is impaired through JNK, which is upregulated by high glucose, and following oxidative stress, which in turn induces stress responses of the cell. Glucagon secretion becomes excessive due to the impaired suppression of its secretion by insulin signaling