Potential role of adenylyl cyclase 8 signaling complexes in regulating insulin secretion from pancreatic beta cells

Glucose-stimulated insulin secretion from pancreatic β cells is mediated by Ca²⁺ influx and amplified by stimulation of GLP-1-receptors through cAMP-based signaling pathways. Interestingly, it has been found that glucose-induced Ca²⁺ signals can induce concurrent adenylyl cyclase isoform 8 (AC8)-mediated cAMP signals and, conversely, that GLP-1-receptor-mediated cAMP signals are able to induce Ca²⁺ signals. In this review, we explore the signaling complexes revolving around AC8 in modulating insulin release, from the initial discovery of the importance of this AC isoform to recent investigations of its interacting molecular partners. We suggest that investigating the structural assembly of the proteins associated with AC8 in β cells might reveal how this particular protein complex could be targeted to modify insulin secretion. Specifically, we suggest that disrupting the protein-protein interaction between A-kinase anchoring protein 79 (AKAP79) and AC8 could lead to disinhibition of AC8 activity and increased insulin secretion. Potentially, AC8 protein interactions could become a future target in type 2 diabetic patients with dysfunction of insulin secretion.