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We performed histological evaluation and gene expression analysis of the pancreatic islets and liver after each treatment and compared the results to those in untreated mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The unsustained hypoglycaemic effect of GKAs was reproduced in\n                      <jats:italic>db\/db<\/jats:italic>\n                      mice in conjunction with significant hepatic fat accumulation. The initial reactions to treatment with the GKA in the liver were upregulation of the gene expression of\n                      <jats:italic>carbohydrate response element\u2010binding protein beta<\/jats:italic>\n                      (\n                      <jats:italic>Chrebp\u2010b<\/jats:italic>\n                      ) and downregulation of\n                      <jats:italic>phosphoenolpyruvate carboxykinase<\/jats:italic>\n                      (\n                      <jats:italic>Pepck<\/jats:italic>\n                      ) on day 1. Subsequently, the initial changes in\n                      <jats:italic>Chrebp\u2010b<\/jats:italic>\n                      and\n                      <jats:italic>Pepck<\/jats:italic>\n                      disappeared and increases in the expression of genes involved in lipogenesis, including\n                      <jats:italic>acetyl\u2010CoA carboxylase<\/jats:italic>\n                      and\n                      <jats:italic>fatty acid synthase<\/jats:italic>\n                      , were observed. There were no significant changes in the pancreatic \u03b2 cells nor in hepatic insulin signalling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The GKA showed an unsustained hypoglycaemic effect and promoted hepatic fat accumulation in\n                      <jats:italic>db\/db<\/jats:italic>\n                      mice. Dynamic changes in the expression of hepatic genes involved in lipogenesis and gluconeogenesis could affect the unsustained hypoglycaemic effect of the GKA despite no changes in pancreatic \u03b2\u2010cell function and mass.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14586","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T03:26:20Z","timestamp":1635305180000},"page":"391-401","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Glucokinase activation leads to an unsustained hypoglycaemic effect with hepatic triglyceride accumulation in\n                    <scp>\n                      <i>db\/db<\/i>\n                    <\/scp>\n                    mice"],"prefix":"10.1111","volume":"24","author":[{"given":"Shinichiro","family":"Kawata","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8192-0006","authenticated-orcid":false,"given":"Akinobu","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5909-3243","authenticated-orcid":false,"given":"Hideaki","family":"Miyoshi","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Obesity, Faculty of Medicine and Graduate School of Medicine Hokkaido University Graduate School of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelaier","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, 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