Gastric Inhibitory Polypeptide and its Receptor are Expressed in the Central Nervous System and Support Neuronal Survival.

The development of neuronal apoptosis depends on an intrinsic transcriptionalprogram. By DNA microarray technology, we have previously implicated a number of genes in different paradigms of neuronal apoptosis. In the present study, weinvestigated the spatiotemporal pattern of expression of two of these genes,gastric inhibitory polypeptide (Gip) and its receptor (Gipr) in the rat centralnervous system. The levels of their transcripts were measured with real-timequantitative polymerase chain reaction and in situ-hybridization. Widespreadexpression of Gip and Gipr was found in adult rat brain, whereas during postnatalcerebellum development, they were highly expressed in the external and internalgranule layer, and in Purkinje cells. To investigate the possible biologicalfunction of Gip we examined its effects in vitro. Addition of Gip to culturedcerebellar granule neurons reduced the extent of apoptotic death induced byswitching the growing medium from 25 to 5 mM K+. This neurotrophic effect wasmimicked by that of PACAP38 and IGF1. We conclude that Gip acts as an endogenous neurotrophic factor and supports neuronal survival.