Therapeutic effects and mechanisms of Xinmaitong formula for type 2 diabetes mellitus via GLP-1R signaling
IntroductionTraditional Chinese Medicine (TCM) theory posits that type 2 diabetes mellitus (T2DM) characterized by Qi and Yin deficiency, is associated with elevated blood lipid levels. The Xinmaitong formula (XMT) is a folk remedy believed to lower blood lipid levels. However, the functional compon...
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Frontiers Media S.A.
2025-04-01
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| author | Weidong Pu Weidong Pu Weidong Pu Yang Pan Yang Pan Yang Pan Kang Yang Kang Yang Kang Yang Jian Gao Jian Gao Jian Gao Fen Tian Fen Tian Fen Tian Jingrui Song Jingrui Song Yubing Huang Yubing Huang Yanmei Li Yanmei Li Yanmei Li |
| author_facet | Weidong Pu Weidong Pu Weidong Pu Yang Pan Yang Pan Yang Pan Kang Yang Kang Yang Kang Yang Jian Gao Jian Gao Jian Gao Fen Tian Fen Tian Fen Tian Jingrui Song Jingrui Song Yubing Huang Yubing Huang Yanmei Li Yanmei Li Yanmei Li |
| author_sort | Weidong Pu |
| collection | DOAJ |
| description | IntroductionTraditional Chinese Medicine (TCM) theory posits that type 2 diabetes mellitus (T2DM) characterized by Qi and Yin deficiency, is associated with elevated blood lipid levels. The Xinmaitong formula (XMT) is a folk remedy believed to lower blood lipid levels. However, the functional components and molecular mechanisms through which XMT exerts its anti-diabetic effects remain to be elucidated. This study aimed to investigate the therapeutic effects and potential mechanisms of XMT in the treatment of T2DM, focusing on the glucagon-like peptide-1 receptor (GLP-1R) signaling pathway.MethodsA TCM formula that promotes GLP-1R expression was screened using a GLP-1R promoter-dependent luciferase reporter gene vector (PGL3-GLP-1R-luc). The T2DM mouse model was established using a high-fat diet and streptozotocin (STZ). Blood glucose levels were measured using a glucometer and oral glucose tolerance test (OGTT). Serum biochemical parameters and insulin levels were also assessed. Organ pathology in mice was evaluated using hematoxylin and eosin (H&E) staining. Immunofluorescence (IF) was employed to observe changes in insulin and GLP-1R expression in the pancreas of mice. The effects of medicated serum on Min6 cell growth were examined using a methyl thiazolyl tetrazolium (MTT) assay. A Min6 cell injury model was established to detect cAMP and Ca2+ concentrations. Ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to identify blood-absorbed components of XMT.ResultsLuciferase reporter constructs driven by GLP-1R promoter response elements analysis identified that TCM formula XMT promoted GLP-1R expression. In vivo experiments demonstrated that XMT significantly reduced fasting blood glucose levels in T2DM mice and improved OGTT results. It also exhibited protective effects on islet tissues, notably increasing GLP-1R expression and insulin secretion in the pancreas. Biochemical markers indicated no significant adverse effects on liver or kidney function following XMT administration. After treatment with palmitic acid (PA), GLP-1R expression in Min6 cells was significantly decreased. However, treatment with XMT upregulated GLP-1R expression. Additionally, cyclic adenosine monophosphate (cAMP) and Ca2+ exhibited substantial improvements, and the key pancreatic growth protein PDX1 was activated.ConclusionXMT exerts hypoglycemic effects by upregulating GLP-1R gene expression, enhancing GLP-1R protein synthesis, and subsequently promoting cAMP release. This process activates Ca2+ influx in pancreatic β-cells, triggering insulin exocytosis from islet cells. |
| format | Article |
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| publishDate | 2025-04-01 |
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| spelling | doaj-art-d47ee8e66bb64bb89a965ba6096923eb2025-08-20T02:08:35ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15754501575450Therapeutic effects and mechanisms of Xinmaitong formula for type 2 diabetes mellitus via GLP-1R signalingWeidong Pu0Weidong Pu1Weidong Pu2Yang Pan3Yang Pan4Yang Pan5Kang Yang6Kang Yang7Kang Yang8Jian Gao9Jian Gao10Jian Gao11Fen Tian12Fen Tian13Fen Tian14Jingrui Song15Jingrui Song16Yubing Huang17Yubing Huang18Yanmei Li19Yanmei Li20Yanmei Li21State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, ChinaNatural Products Research Center of Guizhou Province, Guizhou Medical University, Guiyang, ChinaSchool of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guiyang, Guizhou, ChinaState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, ChinaNatural Products Research Center of Guizhou Province, Guizhou Medical University, Guiyang, ChinaSchool of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guiyang, Guizhou, ChinaState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, ChinaNatural Products Research Center of Guizhou Province, Guizhou Medical University, Guiyang, ChinaSchool of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guiyang, Guizhou, ChinaState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, ChinaNatural Products Research Center of Guizhou Province, Guizhou Medical University, Guiyang, ChinaSchool of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guiyang, Guizhou, ChinaState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, ChinaNatural Products Research Center of Guizhou Province, Guizhou Medical University, Guiyang, ChinaSchool of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guiyang, Guizhou, ChinaState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, ChinaNatural Products Research Center of Guizhou Province, Guizhou Medical University, Guiyang, ChinaState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, ChinaNatural Products Research Center of Guizhou Province, Guizhou Medical University, Guiyang, ChinaState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, ChinaNatural Products Research Center of Guizhou Province, Guizhou Medical University, Guiyang, ChinaSchool of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guiyang, Guizhou, ChinaIntroductionTraditional Chinese Medicine (TCM) theory posits that type 2 diabetes mellitus (T2DM) characterized by Qi and Yin deficiency, is associated with elevated blood lipid levels. The Xinmaitong formula (XMT) is a folk remedy believed to lower blood lipid levels. However, the functional components and molecular mechanisms through which XMT exerts its anti-diabetic effects remain to be elucidated. This study aimed to investigate the therapeutic effects and potential mechanisms of XMT in the treatment of T2DM, focusing on the glucagon-like peptide-1 receptor (GLP-1R) signaling pathway.MethodsA TCM formula that promotes GLP-1R expression was screened using a GLP-1R promoter-dependent luciferase reporter gene vector (PGL3-GLP-1R-luc). The T2DM mouse model was established using a high-fat diet and streptozotocin (STZ). Blood glucose levels were measured using a glucometer and oral glucose tolerance test (OGTT). Serum biochemical parameters and insulin levels were also assessed. Organ pathology in mice was evaluated using hematoxylin and eosin (H&E) staining. Immunofluorescence (IF) was employed to observe changes in insulin and GLP-1R expression in the pancreas of mice. The effects of medicated serum on Min6 cell growth were examined using a methyl thiazolyl tetrazolium (MTT) assay. A Min6 cell injury model was established to detect cAMP and Ca2+ concentrations. Ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to identify blood-absorbed components of XMT.ResultsLuciferase reporter constructs driven by GLP-1R promoter response elements analysis identified that TCM formula XMT promoted GLP-1R expression. In vivo experiments demonstrated that XMT significantly reduced fasting blood glucose levels in T2DM mice and improved OGTT results. It also exhibited protective effects on islet tissues, notably increasing GLP-1R expression and insulin secretion in the pancreas. Biochemical markers indicated no significant adverse effects on liver or kidney function following XMT administration. After treatment with palmitic acid (PA), GLP-1R expression in Min6 cells was significantly decreased. However, treatment with XMT upregulated GLP-1R expression. Additionally, cyclic adenosine monophosphate (cAMP) and Ca2+ exhibited substantial improvements, and the key pancreatic growth protein PDX1 was activated.ConclusionXMT exerts hypoglycemic effects by upregulating GLP-1R gene expression, enhancing GLP-1R protein synthesis, and subsequently promoting cAMP release. This process activates Ca2+ influx in pancreatic β-cells, triggering insulin exocytosis from islet cells.https://www.frontiersin.org/articles/10.3389/fphar.2025.1575450/fullXinmaitong formulaGLP-1RT2DMcAMPCa2+ |
| spellingShingle | Weidong Pu Weidong Pu Weidong Pu Yang Pan Yang Pan Yang Pan Kang Yang Kang Yang Kang Yang Jian Gao Jian Gao Jian Gao Fen Tian Fen Tian Fen Tian Jingrui Song Jingrui Song Yubing Huang Yubing Huang Yanmei Li Yanmei Li Yanmei Li Therapeutic effects and mechanisms of Xinmaitong formula for type 2 diabetes mellitus via GLP-1R signaling Frontiers in Pharmacology Xinmaitong formula GLP-1R T2DM cAMP Ca2+ |
| title | Therapeutic effects and mechanisms of Xinmaitong formula for type 2 diabetes mellitus via GLP-1R signaling |
| title_full | Therapeutic effects and mechanisms of Xinmaitong formula for type 2 diabetes mellitus via GLP-1R signaling |
| title_fullStr | Therapeutic effects and mechanisms of Xinmaitong formula for type 2 diabetes mellitus via GLP-1R signaling |
| title_full_unstemmed | Therapeutic effects and mechanisms of Xinmaitong formula for type 2 diabetes mellitus via GLP-1R signaling |
| title_short | Therapeutic effects and mechanisms of Xinmaitong formula for type 2 diabetes mellitus via GLP-1R signaling |
| title_sort | therapeutic effects and mechanisms of xinmaitong formula for type 2 diabetes mellitus via glp 1r signaling |
| topic | Xinmaitong formula GLP-1R T2DM cAMP Ca2+ |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1575450/full |
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