{"doi":"10.12794/metadc2257722","title":"Glucose-Induced Developmental Delay is Modulated by Insulin Signaling and Exacerbated in Subsequent Glucose-Fed Generations in Caenorhabditis elegans","abstract":"In this study, we have used genetic, cell biological and transcriptomic methods in the nematode C. elegans as a model to examine the impact of glucose supplementation during development. We show that a glucose-supplemented diet slows the rate of developmental progression (termed \"glucose-induced developmental delay\" or GIDD) and induces the mitochondrial unfolded protein response (UPRmt) in wild-type animals. Mutation in the insulin receptor daf-2 confers resistance to GIDD and UPRmt in a daf-16-dependent manner. We hypothesized that daf-2(e1370) animals alter their metabolism to manage excess glucose. To test this, we used RNA-sequencing which revealed that the transcriptomic profiles of glucose-supplemented wildtype and daf-2(e1370) animals are distinct. From this, we identified a set of 27 genes which are both exclusively upregulated in daf-2(e1370) animals fed a glucose-supplemented diet and regulated by daf-16, including a fatty acid desaturase (fat-5), and two insulin-like peptides (ins-16 and ins-35). Mutation of any of these genes suppresses the resistance of daf-2(e1370) to GIDD. Additionally, double mutation of ins-16 and ins-35 in a daf-2(e1370) background results in an increase in constitutive dauer formation which is suppressed by glucose supplementation. Further investigation of the insulin-like peptides revealed that ins-16 mutation in a wild-type background results in upregulation of ins-35 and DAF-16 nuclear translocation regardless of diet; however, unlike daf-2(e1370), this translocation is not associated with resistance to GIDD. Taken together, these data suggest that glucose-supplemented daf-2(e1370) animals maintain developmental trajectory in part through upregulation of specific insulin-like peptide genes and fatty acid desaturation and contribute to a deeper understanding of the mechanisms underlying the resistance of daf-2(e1370) animals to GIDD. We also showed another fascinating aspect of GIDD: it becomes more pronounced in subsequent generations exposed to a glucose-supplemented diet, suggesting that the parental glucose diet has an impact on the developmental progression of their offspring.","journal":"University of North Texas Digital Library (University of North Texas)","year":2023,"id":415597,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1197535,"name":"Saifun Nahar","orcid":"0000-0002-7180-0430","position":0,"is_corresponding":true}],"reference_count":273,"raw_metadata":null,"created_at":"2026-07-19T01:22:12.933438Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}