{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T15:41:17Z","timestamp":1746805277157,"version":"3.40.5"},"reference-count":27,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T00:00:00Z","timestamp":1650672000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Scientific and Technological Special Project of Yunnan Province","award":["2018ZG010","2018ZG013","81760667"],"award-info":[{"award-number":["2018ZG010","2018ZG013","81760667"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2018ZG010","2018ZG013","81760667"],"award-info":[{"award-number":["2018ZG010","2018ZG013","81760667"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2022,4,23]]},"abstract":"<jats:p>Purpose. Insulin receptor (InsR) sensitizers represent a new type of therapeutic agent for the treatment of diabetes, with 2<jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <a:msup>\n                           <a:mrow\/>\n                           <a:mrow>\n                              <a:mo>\u2032<\/a:mo>\n                           <\/a:mrow>\n                        <\/a:msup>\n                     <\/a:math>\n                  <\/jats:inline-formula>-O-methylperlatolic acid (2-O-M) being a potential InsR targeting drug. The purpose of this study was to determine whether 2-O-M functions as an activator of the insulin signaling pathway, regulating glucose hemostasis through the InsR and exerting a glucose-lowering effect in an animal model of diabetes. Methods. SPR-based analyses were used to detect the binding of different concentrations of 2-O-M to the InsR. The protein levels of IR-\u03b2, p-IR, AKT, and p-AKT in Hepa and C2C12 cell lines and liver and muscle tissues were determined by western blotting. Glucose uptake capacity was determined in C2C12 cells. Streptozotocin-induced diabetic mice were randomly divided into four groups: the control, insulin treated, 2-O-M treated, and combined insulin and 2-O-M treated. Mice were injected with 2-O-M or normal saline and the average blood glucose concentration after 120\u2009min, and the serum levels of insulin, glucagon, and C-peptide were measured. Next, qRT-PCR was performed to detect the mRNA expression of genes involved in lipid and glucose metabolism in the liver and muscle tissues. Results. 2-O-M binds to the extracellular domain of the InsR. Moreover, combination treatment with 2-O-M and insulin resulted in significant activation of the insulin signaling pathway in vitro and significant stimulation of the glucose uptake capacity of C2C12 myotubes. In mice with streptozotocin-induced diabetes, 2-O-M significantly prolonged the blood glucose-lowering effect of insulin, significantly reduced the secretion of exogenous insulin, and reduced the blood glucose concentration in vivo. In addition, treatment with 2-O-M alone significantly enhanced the phosphorylation of AKT in muscle tissue, which enhanced glucose uptake in C2C12 myotubes. Further, 2-O-M significantly increased glucagon secretion and enhanced liver gluconeogenesis to prevent hypoglycemia. Conclusion. 2-O-M enhances the hypoglycemic effect of insulin through the insulin signaling pathway and can be used as a complement to insulin. This synergetic effect may lower the required dose of insulin and protect \u03b2 cells.<\/jats:p>","DOI":"10.1155\/2022\/2042273","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T15:22:16Z","timestamp":1650727336000},"page":"1-13","source":"Crossref","is-referenced-by-count":0,"title":["2<a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                     <a:msup>\n                        <a:mrow\/>\n                        <a:mrow>\n                           <a:mo>\u2032<\/a:mo>\n                        <\/a:mrow>\n                     <\/a:msup>\n                  <\/a:math>-O-Methylperlatolic Acid Enhances Insulin-Regulated Blood Glucose-Lowering Effect through Insulin Receptor Signaling Pathway"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6345-6713","authenticated-orcid":true,"given":"Wang","family":"Yinghao","sequence":"first","affiliation":[{"name":"Key Laboratory of Puer Tea 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