{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T20:41:08Z","timestamp":1789245668378,"version":"build-2803163510"},"reference-count":54,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"Shanghai Municipal Key Clinical Specialty"},{"name":"National Key Clinical Specialty","award":["Z155080000004"],"award-info":[{"award-number":["Z155080000004"]}]},{"name":"Shanghai Municipal Health Commission Clinical Research Fund","award":["202540071"],"award-info":[{"award-number":["202540071"]}]},{"name":"National Key Research and Development Plan","award":["2023YFF0713705"],"award-info":[{"award-number":["2023YFF0713705"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Ketone bodies, particularly \u03b2-hydroxybutyrate (3HB), are often elevated in type 1 diabetes (T1D); however, their physiological roles remain unclear. In a low-carbohydrate diet study, patients with insulin-deficient diabetes exhibited reduced fasting blood glucose and increased fasting blood ketone levels, negatively correlated. Another clinical study using continuous glucose and ketone monitoring confirmed inverse glucose\u2013ketone fluctuations. To test causality, we conducted animal and cellular studies. In streptozotocin-induced T1D mice, 7-week oral 3HB administration improved glucose metabolism and alleviated glycogenic hepatopathy. Imaging with 2-deoxy-2-[18F]-fluoro-d-glucose positron emission tomography\/computed tomography demonstrated reduced hepatic and intestinal glucose uptake. Western blotting confirmed 3HB suppressed glucose transporter (sodium\u2013glucose cotransporter 1, GLUT2, GLUT5) overexpression and normalized glycogen metabolism. In vitro, 3HB dose-dependently inhibited glucose transporter expression and glucose uptake in primary hepatocytes and IEC-6 cells. G protein\u2013coupled receptor 109A (GPR109A) serves as the primary receptor for 3HB. Mechanistic studies using the GPR109A inhibitor mepenzolate bromide, the mTOR inhibitor rapamycin, and siRNA-mediated gene silencing revealed that these effects were GPR109A dependent and linked to inhibition of the PI3K\/AKT\/mTOR pathway. Overall, this study provides new insights into the role of ketone bodies in T1D, establishing 3HB as a modulator of glucose homeostasis through GPR109A-mediated suppression of glucose transporters in the liver and intestine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                  <\/jats:sec>","DOI":"10.2337\/db25-1115","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T19:01:56Z","timestamp":1782154916000},"page":"1125-1141","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":1,"title":["\u03b2-Hydroxybutyrate Improves Glucose Metabolism in Streptozotocin-Induced Type 1 Diabetes by Inhibiting Gut and Liver Glucose Transporters via GPR109A"],"prefix":"10.2337","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7313-6054","authenticated-orcid":false,"given":"Shaobo","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine 1 , Shanghai, China"},{"name":"Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology 2 , Luoyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjie","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine 1 , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxiao","family":"Xin","sequence":"additional","affiliation":[{"name":"Jiangxi University of Chinese Medicine 3 , Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine 1 , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Xie","sequence":"additional","affiliation":[{"name":"Jiangxi University of Chinese Medicine 3 , Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shanghai Eighth People\u2019s Hospital 4 , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shanghai Eighth People\u2019s Hospital 4 , Shanghai, 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