{"doi":"10.1016/j.ceca.2025.103093","title":"ER calcium stores contribute to glucose-induced Ca2+ waves and intercellular connectivity in mouse pancreatic islets","abstract":"Defective insulin secretion is a hallmark of diabetes mellitus. Glucose-induced Ca 2+ oscillations are critical for the stimulation of insulin secretion, though the mechanisms through which these propagate across the islet are poorly understood. Here, we use beta cell-targeted GCaMP6f to explore the role of endoplasmic reticulum (ER) Ca 2+ mobilization in response to submaximal (11mM) or hyperglycemic (25mM) glucose, mimicking diabetes. Inhibition of inositol 1,4,5-trisphosphate (IP 3 ) receptors, and other ion channels, with 2-aminoethoxydiphenyl borate (2-APB), had minimal effects on the initial peak or intercellular connectivity provoked by 11mM glucose. However, 2-APB lowered subsequent glucose-induced cytosolic Ca 2+ increases and connectivity at both 11 and 25mM glucose. Unexpectedly, the activation of IP 3 receptors with the muscarinic acetylcholine receptor agonist carbachol had minimal impact on the initial peak elicited by 11 mM glucose, but Ca 2+ waves at 11 and 25 mM glucose were more poorly coordinated. To determine whether ER calcium mobilization was sufficient to initiate Ca 2+ waves we next blocked sarco(endo)plasmic Ca 2+ ATPase (SERCA) pumps with thapsigargin, whilst preventing plasma membrane depolarization with the K ATP -channel opener, diazoxide. Under these conditions, an initial cytosolic Ca 2+ increase was followed by secondary Ca 2+ waves that subsided slowly. The application of carbachol alongside diazoxide still enhanced Ca 2+ dynamics, though activity was uncoordinated. After genetic deletion of SERCA2 in beta cells, Ca 2+ wave frequency, but not connectivity, were lowered. Our results show that ER Ca 2+ mobilization plays a relatively minor role in the initiation and propagation of Ca 2+ waves in response to glucose but is needed for sustained Ca 2+ waves.","journal":"Cell Calcium","year":2025,"id":549308,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1332180,"name":"Karen Dakessian","orcid":null,"position":1,"is_corresponding":false},{"id":1332181,"name":"AUDREY PROVENCHER-GIRARD","orcid":null,"position":2,"is_corresponding":false},{"id":380698,"name":"William E. Louch","orcid":"0000-0002-0511-6112","position":3,"is_corresponding":false},{"id":350920,"name":"Guy A. Rutter","orcid":"0000-0001-6360-0343","position":4,"is_corresponding":false},{"id":996984,"name":"Luis Fernando Delgadillo-Silva","orcid":"0000-0002-2721-5920","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:54:07.823422Z","pmid":"41418583","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":[]}