Expression analysis and possible functional roles of semaphorin/plexin/CRMP families in mouse pancreatic islets.

Semaphorins were initially identified as axon guidance molecules that were widely expressed and involved in divergent functions in various organs, including neuronal development and immunological processes. Collapsin response mediator proteins (CRMPs) are involved in the intracellular signaling of semaphorin 3A (Sema3a) and are highly expressed in the nervous system. However, the participation of semaphorins or their receptors plexins and CRMPs in the regulation of islet function remains unknown. In this study, we measured the expression of semaphorin, plexin, and CRMP families in mouse islets, and their expression levels were altered by treatment with high glucose or a glucokinase activator (GKA). The expression and phosphorylation of CRMP-2 in islets were upregulated in high-fat diet (HF)-fed obese mice, and the expression of CRMP-2 was downregulated in islets from db/db mice. HF-fed CRMP-2 knockout mice exhibited impaired glucose tolerance. These results indicated that the semaphorin/plexin/CRMP families in mouse islets might be involved in glucose metabolism partly through glucose/glucokinase.