{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:05:47Z","timestamp":1781715947681,"version":"3.54.5"},"reference-count":41,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82070852"],"award-info":[{"award-number":["No. 82070852"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82270901"],"award-info":[{"award-number":["No. 82270901"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Pancreatic \u03b2-cells play a central role in type 2 diabetes mellitus (T2DM), yet the interactions between \u03b2-cells and stromal components within the islet microenvironment remain poorly defined. We investigated the contribution of pancreatic fibroblasts to \u03b2-cell dysfunction and T2DM progression. We used single-cell sequencing technology and in\u00a0vitro experiments to investigate the mechanisms by which bariatric surgery ameliorates T2DM. We introduce the novel concept of a \u201cmetabolic synapse\u201d to describe the interaction between pancreatic fibroblasts and \u03b2-cells. Our findings reveal that pancreatic fibroblasts secrete excessive glutamate in the early stages of T2DM. Elevated glutamate concentrations within the islet microenvironment subsequently activate N-methyl-d-aspartic acid receptors (NMDARs), triggering PANoptosis in pancreatic \u03b2-cells and accelerating T2DM progression. Consistent with this, significant changes in NMDAR expression were observed in human pancreatic samples from patients with T2DM. These findings uncover a previously unrecognized fibroblast\u2013\u03b2-cell communication pathway in the islet niche, provide mechanistic insights into T2DM pathogenesis, and highlight the glutamate\u2013NMDAR axis as a potential therapeutic target for nonsurgical intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>We identify a fibroblast\u2013\u03b2-cell \u201cmetabolic synapse\u201d in type 2 diabetes that couples stromal glutamate overflow to\u2013\u03b2-cell N-methyl-d-aspartic acid receptor (NMDAR) activation. Single-cell maps and coculture assays show diabetogenic stress drives fibroblasts to hypersecrete glutamate, whereas \u03b2-cells upregulate NMDARs, triggering PANoptosis. In rodents, pharmacologic NMDAR blockade attenuates \u03b2-cell PANoptosis, preserves islet function, and improves glycemic control. Human pancreatic samples cohorts reveal fibrosis regression and stage-wise NMDAR upregulation, highlighting the glutamate\u2013NMDAR axis as a therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0863","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T17:12:31Z","timestamp":1771348351000},"page":"661-675","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Activation of the Pancreatic \u201cMetabolic Synapse\u201d Aggravates Type 2 Diabetes Mellitus by Inducing PANoptosis in \u03b2-Cells"],"prefix":"10.2337","volume":"75","author":[{"given":"Zhao","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of General Surgery, Qilu Hospital of Shandong University , Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Zitian","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Qilu Hospital of Shandong University , Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Guangwei","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Qilu Hospital of Shandong University , Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2912-8046","authenticated-orcid":false,"given":"Dong","family":"Shuohui","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Qilu Hospital of Shandong University , Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7474-3276","authenticated-orcid":false,"given":"Wang","family":"Kexin","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Qilu Hospital of Shandong University , Jinan, 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