{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:59:29Z","timestamp":1787018369966,"version":"build-2736575974"},"reference-count":66,"publisher":"American Society for Clinical Investigation","issue":"23","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":76,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DK067528"],"award-info":[{"award-number":["DK067528"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:p>\n                    Type 2 diabetes affects more than 38 million people in the United States, and a major complication is kidney disease. During the analysis of lipotoxicity in diabetic kidney disease, global fatty acid transport protein 2 (FATP2) gene deletion was noted to markedly reduce plasma glucose in db\/db mice due to sustained insulin secretion. To identify the mechanism, we observed that islet FATP2 expression was restricted to \u03b1 cells and that \u03b1 cell FATP2 was functional. Basal glucagon and alanine-stimulated gluconeogenesis were reduced in FATP2-KO db\/db mice compared with db\/db mice. Direct evidence of FATP2-KO\u2013induced \u03b1 cell\u2013mediated glucagon-like peptide 1 (GLP-1) secretion included increased GLP-1\n                    <jats:sup>+<\/jats:sup>\n                    \u03b1 cell mass in FATP2-KO db\/db mice, small-molecule FATP2 inhibitor enhancement of GLP-1 secretion in \u03b1TC1-6 cells and human islets, and exendin[9-39]-inhibitable insulin secretion in FATP2 inhibitor\u2013treated human islets. FATP2-dependent enteroendocrine GLP-1 secretion was excluded by demonstration of similar glucose tolerance and plasma GLP-1 concentrations in db\/db FATP2-KO mice following oral versus i.p. glucose loading, nonoverlapping FATP2 and preproglucagon mRNA expression, and lack of FATP2 and GLP-1 coimmunolocalization in the intestines. We conclude that FATP2 deletion or inhibition exerts glucose-lowering effects through \u03b1 cell\u2013mediated GLP-1 secretion and paracrine \u03b2 cell insulin release.\n                  <\/jats:p>","DOI":"10.1172\/jci192011","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T16:00:48Z","timestamp":1758038448000},"source":"Crossref","is-referenced-by-count":2,"title":["Fatty acid transport protein 2 inhibition enhances glucose tolerance through \u03b1 cell\u2013mediated GLP-1 secretion"],"prefix":"10.1172","volume":"135","author":[{"given":"Shenaz","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Gaivin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve University School of 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