{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T19:49:06Z","timestamp":1792439346523,"version":"4.5.0"},"reference-count":65,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To critically evaluate how communication between the endocrine and exocrine pancreas contributes to diabetes and to distinguish whole\u2010pancreas involvement from mechanistically demonstrated crosstalk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a narrative review of anatomical, imaging, histological, molecular and experimental evidence on endocrine\u2013exocrine communication, prioritising recent primary human and mechanistic studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Islets and exocrine tissue communicate through local vascular, neural, stromal and extracellular matrix routes. Diabetes is associated with distinct whole\u2010pancreas phenotypes: type 1 diabetes (T1D) shows reduced pancreatic volume, acinar loss, exocrine immune infiltration and periductal or perivascular fibrosis, whereas type 2 diabetes (T2D) more often shows acinar\u2010to\u2010ductal metaplasia, lobular or parenchymal fibrosis, angiopathy and increased pancreatic fat fraction on imaging, although histological adiposity is inconsistent. The strongest mechanistic evidence supports insulin\u2010mediated acinar protection, acinar protease effects on \u03b2\u2010cells and transfer of mutant carboxyl ester lipase in maturity\u2010onset diabetes of the young type 8 (MODY8), while stromal, matrix and immune signals represent important but less fully validated amplifying pathways. In T1D and T2D, crosstalk most plausibly acts as a stage\u2010dependent amplifier rather than a universal initiating event.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Diabetes should be studied as a multicellular pancreatic disorder without interpreting associated pathology as evidence of causation. Longitudinal human studies and multicellular models that allow selective perturbation are required to identify clinically actionable interactions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dme.70505","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T19:19:46Z","timestamp":1792437586000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Islet\u2013exocrine crosstalk in diabetes: Distinguishing whole\u2010pancreas pathology from causal communication"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7600-1478","authenticated-orcid":false,"given":"Sophia","family":"Bigot","sequence":"first","affiliation":[{"name":"Centre for Biomedicine Hull York Medical School (HYMS), University of Hull  Hull UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0685-8564","authenticated-orcid":false,"given":"Amin","family":"Ardestani","sequence":"additional","affiliation":[{"name":"Centre for Biomedicine Hull York Medical School (HYMS), University of Hull  Hull UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2022.904004","article-title":"Exocrine\u2010endocrine crosstalk: the influence of pancreatic cellular communications on organ growth, function and disease","volume":"13","author":"Overton DL","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"4","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.2337\/db22-0942","article-title":"Integrated physiology of the exocrine and endocrine compartments in pancreatic diseases: workshop 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