Therapeutic effects and mechanisms of Xinmaitong formula for type 2 diabetes mellitus via GLP-1R signaling

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 9, 2025

Traditional 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) a folk remedy believed to lower However, the functional components molecular mechanisms through which XMT exerts its anti-diabetic effects remain be elucidated. This study aimed investigate therapeutic potential of in treatment T2DM, focusing on glucagon-like peptide-1 receptor (GLP-1R) signaling pathway. A TCM promotes GLP-1R expression was screened using promoter-dependent luciferase reporter gene vector (PGL3-GLP-1R-luc). T2DM mouse model established high-fat diet streptozotocin (STZ). Blood glucose levels were measured glucometer oral tolerance test (OGTT). Serum biochemical parameters insulin also assessed. Organ pathology mice evaluated hematoxylin eosin (H&E) staining. Immunofluorescence (IF) employed observe changes pancreas mice. medicated serum Min6 cell growth examined methyl thiazolyl tetrazolium (MTT) assay. injury detect cAMP Ca2+ concentrations. Ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) used identify blood-absorbed XMT. Luciferase constructs driven promoter response elements analysis identified promoted expression. In vivo experiments demonstrated significantly reduced fasting improved OGTT results. It exhibited protective islet tissues, notably increasing secretion pancreas. Biochemical markers indicated no significant adverse liver or kidney function following administration. After palmitic acid (PA), cells decreased. upregulated Additionally, cyclic adenosine monophosphate (cAMP) substantial improvements, key pancreatic protein PDX1 activated. hypoglycemic upregulating expression, enhancing synthesis, subsequently promoting release. process activates influx β-cells, triggering exocytosis from cells.

Language: Английский

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Enhancing Diabetes Treatment: Comparing Pioglitazone/Metformin with Dapagliflozin Versus Basal Insulin/Metformin in Type 2 Diabetes

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 1795 - 1808

Published: March 1, 2025

Aim: The aim of this study was to compare the efficacy and safety fixed-dose combination (FDC) pioglitazone metformin supplemented with dapagliflozin (test group) those basal insulin (control in patients inadequately controlled type 2 diabetes mellitus (T2DM). Methods: This 16-week, prospective, randomized, open-label enrolled aged 18– 75 years glycated hemoglobin (HbA1c) levels between ≥ 8% ≤ 11%. primary endpoint proportion who achieved HbA1c < 7% at week 16 without hypoglycemia or weight gain. secondary endpoints included blood glucose, lipid profile, body weight, mass index, inflammatory markers, bone Gla-protein, liver enzymes, patient satisfaction. Results: Among full analysis set 147 participants, no significant difference observed test group control group. However, had a higher percentage experienced loss 3% (31.51% vs 13.51%, P =0.009). Patients whose BMI≥ 24 kg/m also substantial achievement rate (36.73% 15.79%, =0.014). exhibited greater reduction improvements 2-hour postprandial glucose level, systolic pressure, profile. Notably, therapy did not increase risk were more satisfied than continuing accept pioglitazone/metformin FDC combined dapagliflozin. Conclusion: In absence contraindications, may serve as safe effective alternative for rectifying inadequate control, former enables metabolic compromising safety. Chinese Clinical Trial Registry Number: CHiCTR 2000036076 . https://www.chictr.org.cn/showproj.html?proj=58825 Keywords: dapagliflozin, FDC, diabetes, metformin,

Language: Английский

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Pioglitazone with SGLT2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes and non-alcoholic fatty liver disease: could the combinations of an old friend with new players yield better outcomes?

Archives of Medical Science - Atherosclerotic Diseases, Journal Year: 2025, Volume and Issue: 10(1), P. 1 - 15

Published: March 14, 2025

More than 25% of the adult population worldwide and approximately 50–75% patients with type 2 diabetes are diagnosed non-alcoholic fatty liver disease. Insulin resistance is one most crucial factors underlying its pathogenesis a significant determinant progression to steatohepatitis. The complex pathophysiology disease emphasizes need for combination treatment strategies drug classes that target different cellular pathways, since no single agent can control all mechanisms contributing development evolution. Pioglitazone, main thiazolidinedione in clinical practice, only true insulin sensitizing antidiabetic our therapeutic armamentarium diabetes. Current international practice guidelines recommend PIO as promising therapy who experience NASH GLP-1 receptor agonists SGLT2 inhibitors have shown salutary cardiometabolic renal effects diabetes, well beneficial activities those This review discusses pathophysiological background use these three categories It also explores thoroughly combinations pioglitazone either or inhibitors, their future role this setting.

Language: Английский

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Efficacy and Safety of Pioglitazone Add-on in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin and Dapagliflozin: A Multicenter, Randomized, Double-blind, and Placebo-Controlled Study

Clinical Therapeutics, Journal Year: 2024, Volume and Issue: 46(9), P. 662 - 669

Published: July 26, 2024

Language: Английский

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