{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T04:53:37Z","timestamp":1779944017129,"version":"3.53.1"},"reference-count":11,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100007206","name":"Vanderbilt Institute for Clinical and Translational Research","doi-asserted-by":"publisher","award":["UL1-TR000445"],"award-info":[{"award-number":["UL1-TR000445"]}],"id":[{"id":"10.13039\/100007206","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institute for Translational Medicine","award":["UL1-TR000430"],"award-info":[{"award-number":["UL1-TR000430"]}]},{"name":"Vanderbilt University Institute of Imaging Sciences","award":["1S10OD021771-01"],"award-info":[{"award-number":["1S10OD021771-01"]}]},{"name":"The Leona M. and Harry B. Helmsley Charitable Trust, the Juvenile Diabetes Research Foundation, the Doris Duke Charitable Foundation, the National Institutes of Health","award":["DK104942"],"award-info":[{"award-number":["DK104942"]}]},{"name":"The Leona M. and Harry B. Helmsley Charitable Trust, the Juvenile Diabetes Research Foundation, the Doris Duke Charitable Foundation, the National Institutes of Health","award":["DK129979"],"award-info":[{"award-number":["DK129979"]}]},{"name":"Vanderbilt and Chicago Diabetes Research and Training Centers","award":["DK20593"],"award-info":[{"award-number":["DK20593"]}]},{"name":"Vanderbilt and Chicago Diabetes Research and Training Centers","award":["DK20595"],"award-info":[{"award-number":["DK20595"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4,1]]},"abstract":"<jats:sec><jats:title>OBJECTIVE<\/jats:title><jats:p>To determine the mechanism of reduced pancreas size in type 1 diabetes and the significance of islet-derived insulin in pancreatic growth.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESEARCH DESIGN AND METHODS<\/jats:title><jats:p>Using a validated and standardized MRI protocol, we measured pancreas volume and shape in a family with an autosomal-dominant insulin gene mutation that results in insulin deficiency similar in severity to that of type 1 diabetes but without autoimmunity. DNA sequencing confirmed the mutation in all four affected individuals and none of the four control family members. Insulin secretory capacity was determined by measuring postprandial urinary C-peptide.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Family members with this form of monogenic diabetes had a markedly smaller pancreas and a severely impaired postprandial C-peptide level than family members without diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>These results suggest that severe insulin deficiency, rather than islet-directed autoimmunity, leads to reduced pancreas size in type 1 diabetes and that insulin is a major trophic factor for the exocrine pancreas.<\/jats:p><\/jats:sec>","DOI":"10.2337\/dc22-2082","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T20:15:00Z","timestamp":1675282500000},"page":"773-776","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":21,"title":["Insulin Deficiency From Insulin Gene Mutation Leads to Smaller Pancreas"],"prefix":"10.2337","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2043-0150","authenticated-orcid":false,"given":"Jordan J.","family":"Wright","sequence":"first","affiliation":[{"name":"1Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-2950","authenticated-orcid":false,"given":"Jonathan M.","family":"Williams","sequence":"additional","affiliation":[{"name":"1Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9465-4870","authenticated-orcid":false,"given":"Lisa R.","family":"Letourneau-Freiberg","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balamurugan","family":"Kandasamy","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetra","family":"Reyes","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9961-6398","authenticated-orcid":false,"given":"Anastasia Gant","family":"Kanegusuku","sequence":"additional","affiliation":[{"name":"3Department of Pathology, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Philipson","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siri Atma W.","family":"Greeley","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3662-6692","authenticated-orcid":false,"given":"Melissa A.","family":"Hilmes","sequence":"additional","affiliation":[{"name":"4Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN"},{"name":"5Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1941-5786","authenticated-orcid":false,"given":"Alvin C.","family":"Powers","sequence":"additional","affiliation":[{"name":"1Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN"},{"name":"6Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN"},{"name":"7VA Tennessee Valley Healthcare System, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3413-8801","authenticated-orcid":false,"given":"John","family":"Virostko","sequence":"additional","affiliation":[{"name":"8Department of Diagnostic Medicine, Dell Medical School, University of Texas at Austin, Austin, TX"},{"name":"9Livestrong Cancer Institutes, Dell Medical School, University of Texas at Austin, Austin, TX"},{"name":"10Department of Oncology, Dell Medical School, University of Texas at Austin, Austin, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6889-9345","authenticated-orcid":false,"given":"Daniel J.","family":"Moore","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL"},{"name":"11Department of Pathology, Immunology, and Microbiology, Vanderbilt University, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"key":"2023032318550339300_","doi-asserted-by":"crossref","first-page":"248","DOI":"10.2337\/dc18-1507","article-title":"Pancreas volume declines during the first year after diagnosis of type 1 diabetes and exhibits altered diffusion at disease onset","volume":"42","author":"Virostko","year":"2019","journal-title":"Diabetes Care"},{"key":"2023032318550339300_","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2337\/dc18-1512","article-title":"Relative pancreas volume is reduced in first-degree relatives of patients with type 1 diabetes","volume":"42","author":"Campbell-Thompson","year":"2019","journal-title":"Diabetes Care"},{"key":"2023032318550339300_","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1007\/s00125-020-05155-y","article-title":"Decreased pancreatic acinar cell number in type 1 diabetes","volume":"63","author":"Wright","year":"2020","journal-title":"Diabetologia"},{"key":"2023032318550339300_","unstructured":"Multicenter Assessment of the Pancreas in Type 1 Diabetes . About MAP-T1D. Accessed 27 January 2023. Available from https:\/\/www.map-t1d.com"},{"key":"2023032318550339300_","doi-asserted-by":"crossref","first-page":"e0256029","DOI":"10.1371\/journal.pone.0256029","article-title":"Development of a standardized MRI protocol for pancreas assessment in humans","volume":"16","author":"Virostko","year":"2021","journal-title":"PloS One"},{"key":"2023032318550339300_","doi-asserted-by":"crossref","first-page":"286","DOI":"10.2337\/dc10-1293","article-title":"Urinary C-peptide creatinine ratio is a practical outpatient tool for identifying hepatocyte nuclear factor 1-alpha\/hepatocyte nuclear factor 4-alpha maturity-onset diabetes of the young from long-duration type 1 diabetes","volume":"34","author":"Besser","year":"2011","journal-title":"Diabetes Care"},{"key":"2023032318550339300_","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.2337\/db07-1405","article-title":"Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood","volume":"57","author":"Edghill","year":"2008","journal-title":"Diabetes"},{"key":"2023032318550339300_","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.2337\/db19-1034","article-title":"Integrated pancreatic blood flow: bidirectional microcirculation between endocrine and exocrine pancreas","volume":"69","author":"Dybala","year":"2020","journal-title":"Diabetes"},{"key":"2023032318550339300_","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/BF00400628","article-title":"In situ binding of islet hormones in the isolated perfused rat pancreas: evidence for local high concentrations of islet hormones via the islet-acinar axis","volume":"38","author":"Nakagawa","year":"1995","journal-title":"Diabetologia"},{"key":"2023032318550339300_","doi-asserted-by":"crossref","first-page":"eabh2169","DOI":"10.1126\/sciadv.abh2169","article-title":"A single-cell type transcriptomics map of human tissues","volume":"7","author":"Karlsson","year":"2021","journal-title":"Sci Adv"},{"key":"2023032318550339300_","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1053\/j.gastro.2020.11.010","article-title":"Single-nucleus and in situ RNA-sequencing reveal cell topographies in the human pancreas","volume":"160","author":"Tosti","year":"2021","journal-title":"Gastroenterology"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/46\/4\/773\/700591\/dc222082.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/46\/4\/773\/700591\/dc222082.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T01:14:35Z","timestamp":1701825275000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/46\/4\/773\/148385\/Insulin-Deficiency-From-Insulin-Gene-Mutation"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,1]]},"references-count":11,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2,1]]},"published-print":{"date-parts":[[2023,4,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc22-2082","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,1]]}}}