Despite the notable plant protective role, many herbivorous insects have evolved various resistance strategies to evade plant defense, and the front line of battle is the digestive canal. Consistently, our microarray analyses demonstrated that the midgut gene expression program in cowpea bruchids changes in SAR131675 response to dietary challenges, whether the challenge was derived from scN or bergapten. Genome-wide resource reallocation is perhaps an accommodation essential for insect survival. Among bergapteninduced genes are P450, GST, CAT and LAC2 genes, known to encode allelochemical-detoxifying enzymes that confer metabolic resistance, or phenoloxidase that possibly increases resistance to penetration of bergapten. Thus it is a logical assumption that transcriptomic reconfiguration contributes to mitigating the toxic effect of plant defensive metabolites. While some P450 genes are induced, others are down-regulated. This differential response possibly reflects the large number, different substrate specificity and diverse functions that P450s may possess in cowpea bruchids. Bergapten can inhibit the housefly CYP6D1 gene, while it also serves as the substrate of other P450s. In addition to detoxification of xenobiotics including plant secondary metabolites and synthetic pesticides, P450s control TH-302 synthesis and degradation of insect hormones, and thus play important roles in insect growth and development. Delayed development in response to dietary bergapten is in agreement with altered development regulatory genes, such as JH esterases or JH epoxide hydrolases. It is well established that furanocoumarins induce phototoxicity in many insects that feed on diets containing these compounds, by producing reactive oxygen species. Although cowpea bruchid larvae feed inside the seeds and are therefore shielded from most direct light, shelf light in our insect-rearing chamber could have penetrated the seeds to a certain extent and resulted in some levels of oxidative stress. The notion that phototoxicity may have contributed to the overall anti-insect activity we observed is supported by the induction of LAC2 by bergapten. LAC2 is required for cuticle sclerotization and egg chorion tanning. Protection from phototoxins by pigmentation has been known to occur in mammals and in insects. Induction of cowpea bruchid LAC2 could result from insect response to phototoxicity, although furanocoumarins are antifeedants to insects even in the absence of light. One of the highly induced genes revealed by our microarray study encodes the antifungal peptide drosomycin, suggesting the involvement of insect immunity in response to dietary challenges. Cross-talk between immune response and other stress responses, and pathway convergence in general, is becoming an emerging theme that has been discussed recently in both vertebrates and invertebrates. For instance, starvation can induce antimicrobial peptide genes in non-infected or immunity-defective insects through activating a transcription factor FOXO, independent of pathogen responsive pathways.