{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:42:35Z","timestamp":1772160155540,"version":"3.50.1"},"reference-count":68,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To achieve glucose\u2010activated transcriptional regulation of insulin analogue in skeletal muscle of T1D mice, thereby controlling blood glucose levels and preventing or mitigating diabetes\u2010related complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      We developed the GANIT (\n                      <jats:italic>G<\/jats:italic>\n                      lucose\u2010\n                      <jats:italic>A<\/jats:italic>\n                      ctivated\n                      <jats:italic>N<\/jats:italic>\n                      FAT\u2010regulated\n                      <jats:italic>I<\/jats:italic>\n                      NSA\u2010F\n                      <jats:italic>T<\/jats:italic>\n                      ranscription) system, an innovative platform building upon the previously established intramuscular plasmid DNA (pDNA) delivery and expression system. In the GANIT system, skeletal muscle cells are genetically engineered to endogenously produce the insulin analogue INSA\u2010F (\n                      <jats:italic>Ins<\/jats:italic>\n                      ulin\n                      <jats:italic>A<\/jats:italic>\n                      spart with\n                      <jats:italic>F<\/jats:italic>\n                      urin cleavage sites). The transcription of INSA\u2010F is precisely controlled by a glucose\u2010responsive promoter containing NFAT (Nuclear Factor of Activated T\u2010cells) regulatory motifs, which can be activated in response to changes in extracellular glucose concentrations. This design enables glucose\u2010dependent regulation of insulin analogue expression, mimicking physiological glucose\u2010responsive insulin secretion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>T1D mice that received two GANIT treatments over a 2\u2010month experimental period demonstrated significant improvements in glucose homeostasis, glucose tolerance and glycated haemoglobin (HbA1c) levels. Additionally, the treatment effectively reduced oxidative stress and alleviated cardiac and renal fibrosis, while maintaining a favourable biosafety profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The GANIT system provides significant advantages in terms of efficiency, convenience and cost\u2010effectiveness, making it a promising approach for regulating blood glucose levels and alleviating diabetes\u2010related complications in insulin\u2010deficient diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.16197","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:37:47Z","timestamp":1736815067000},"page":"2044-2058","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long\u2010term blood glucose control via glucose\u2010activated transcriptional 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