KDT501, a derivative from hops, normalizes glucose metabolism and body weight in rodent models of diabetes
| Autor: | Anuradha Desai, Neile Grayson, Veera Konda, Gary Darland, Jeffrey S. Bland |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Blood Glucose
Male Mouse medicine.medical_treatment lcsh:Medicine Mice Obese Gene Expression Biochemistry Monocytes Mice Endocrinology Drug Discovery Molecular Cell Biology Adipocytes Insulin lcsh:Science Cells Cultured Multidisciplinary biology Chemistry Animal Models Metformin Medicine Rosiglitazone medicine.drug Research Article medicine.medical_specialty Immune Cells Immunology Humulus Carbohydrate metabolism Diabetes Mellitus Experimental Insulin resistance Model Organisms In vivo Diabetes mellitus Internal medicine medicine Animals Humans Hypoglycemic Agents Obesity Biology Triglycerides Nutrition Glycated Hemoglobin Inflammation Diabetic Endocrinology Pioglitazone Macrophages lcsh:R Body Weight Immunity Diabetes Mellitus Type 2 biology.organism_classification medicine.disease Lipid Metabolism Rats Rats Zucker Mice Inbred C57BL PPAR gamma Glucose Metabolism Diabetes Mellitus Type 2 Rat lcsh:Q Thiazolidinediones Insulin Resistance |
| Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 1, p e87848 (2014) |
| ISSN: | 1932-6203 |
| Popis: | AIMS/HYPOTHESIS: We developed KDT501, a novel substituted 1,3-cyclopentadione chemically derived from hop extracts, and evaluated it in various in vitro and in vivo models of diabetes and insulin sensitivity. METHODS: KDT501 was evaluated for anti-inflammatory effects in monocyte/macrophage cells; agonistic activity for peroxisome proliferator-activated receptors (PPAR); lipogenesis and gene expression profile in human subcutaneous adipocytes. Body composition, glucose, insulin sensitivity, and lipids were assessed in diet-induced obesity (DIO) mice and Zucker Diabetic Fatty (ZDF) rats after oral administration. RESULTS: KDT501 mediated lipogenesis in 3T3L1 and human subcutaneous adipocytes; however, the gene expression profile of KDT501 differed from that of the full PPARγ agonist rosiglitazone, suggesting that KDT501 has pleiotropic biological activities. In addition, KDT501 showed only modest, partial PPARγ agonist activity and exhibited anti-inflammatory effects in monocytes/macrophages that were not observed with rosiglitazone. In a DIO mouse model, oral administration of KDT501 significantly reduced fed blood glucose, glucose/insulin AUC following an oral glucose bolus, and body fat. In ZDF rats, oral administration of KDT501 significantly reduced fed glucose, fasting plasma glucose, and glucose AUC after an oral glucose bolus. Significant, dose-dependent reductions of plasma hemoglobin A1c, weight gain, total cholesterol, and triglycerides were also observed in animals receiving KDT501. CONCLUSION: These results indicate that KDT501 produces a unique anti-diabetic profile that is distinct in its spectrum of pharmacological effects and biological mechanism from both metformin and pioglitazone. KDT501 may thus constitute a novel therapeutic agent for the treatment of Type 2 diabetes and associated conditions. |
| Databáze: | OpenAIRE |
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