Small Molecule Kaempferol Promotes Insulin Sensitivity and Preserved Pancreatic β-Cell Mass in Middle-Aged Obese Diabetic Mice
| Autor: | Kyung-Shin Suh, Mostafa M. Ali, Dongmin Liu, Yanling Zhang, Hana Alkhalidy, Matthew W. Hulver, Zhenquan Jia, Zhiyong Cheng, Aihua Wang, William T. Moore, Ryan P. McMillan, Wei Zhen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
endocrine system diseases Article Subject Endocrinology Diabetes and Metabolism Glucose uptake medicine.medical_treatment 030209 endocrinology & metabolism lcsh:Diseases of the endocrine glands. Clinical endocrinology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Insulin resistance Internal medicine medicine Hyperinsulinemia Glycogen synthase 030304 developmental biology 2. Zero hunger 0303 health sciences lcsh:RC648-665 biology Insulin medicine.disease Streptozotocin 3. Good health chemistry biology.protein Kaempferol GLUT4 medicine.drug Research Article |
| Zdroj: | Journal of Diabetes Research Journal of Diabetes Research, Vol 2015 (2015) |
| ISSN: | 2314-6745 |
| DOI: | 10.1155/2015/532984 |
| Popis: | Insulin resistance and a progressive decline in functionalβ-cell mass are hallmarks of developing type 2 diabetes (T2D). Thus, searching for natural, low-cost compounds to target these two defects could be a promising strategy to prevent the pathogenesis of T2D. Here, we show that dietary intake of flavonol kaempferol (0.05% in the diet) significantly ameliorated hyperglycemia, hyperinsulinemia, and circulating lipid profile, which were associated with the improved peripheral insulin sensitivity in middle-aged obese mice fed a high-fat (HF) diet. Kaempferol treatment reversed HF diet impaired glucose transport-4 (Glut4) and AMP-dependent protein kinase (AMPK) expression in both muscle and adipose tissues from obese mice.In vitro, kaempferol increased lipolysis and prevented high fatty acid-impaired glucose uptake, glycogen synthesis, AMPK activity, and Glut4 expression in skeletal muscle cells. Using another mouse model of T2D generated by HF diet feeding and low doses of streptozotocin injection, we found that kaempferol treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in obese diabetic mice, which are associated with the improved isletβ-cell mass. These results demonstrate that kaempferol may be a naturally occurring anti-diabetic agent by improving peripheral insulin sensitivity and protecting against pancreaticβ-cell dysfunction. |
| Databáze: | OpenAIRE |
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