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8. Effects of ibuprofen in the ZDF rat model of type 2 diabetes
| 發布日期:2024-06-12 | 更新日期: 發布單位:

Effects of ibuprofen in the ZDF rat model of type 2 diabetes

Alexander Gosslaua,e*, Unsal Ozdogrub , Emmanuel Zachariahc , Shiming Lid,

e and Chi-Tang Hoe

a Department of Science (Biology), City University of New York, BMCC, New York, NY10007

b Department of Information and Decisions Sciences, University of Illinois at Chicago, Chicago, Illinois 60607

c Oncopath Genomics, Monmouth Junction, New Jersey08852

d Huanggang Normal University, College of Life Science; Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization; Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains; Hubei Zhongke Research Institute of Industrial Technology, Huanggang, 438000, Hubei Province, China

e Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901-8520

We aimed to investigate the therapeutic potential of ibuprofen against type 2 diabetes (T2D) using obese Zucker diabetic fatty (ZDF) rats as type 2 diabetes model. ZDF rats were hyperglycemic, dyslipidemic and expressed pro-inflammatory markers in contrast to lean controls, thus reflecting the relationship between obesity and chronic inflammation promoting T2D. Chronic treatment with ibuprofen (2-(4-Isobutylphenyl)propanoic acid) was used to study the impact on pathological T2D conditions as compared to metformin (1,1-dimethylbiguanide) treated ZDF as well as lean controls. Ibuprofen decreased A1c but induced a high insulin release with improved glucose tolerance only after early time points (i.g., 15 and 30 min) resulting in a non-significant decline of AUC values and translating into a high HOMA-IR. In addition, ibuprofen significantly lowered cholesterol, free fatty acids and HDL-C. Some of these effects by ibuprofen might be based on its anti- inflammatory effects through inhibition of cytokine/chemokine signaling (i.g., COX-2, ICAM-1 and TNF-α) as measured in whole blood and epididymal adipose tissue by TaqMan and/or upregulation of anti-inflammatory cytokines (i.g., IL-4 and IL-13) by ELISA analysis in blood. In conclusion, our ZDF animal study showed positive effects of ibuprofen against diabetic complications such as inflammation and dyslipidemia but also demonstrated the risk of causing insulin resistance.

Keywords: Ibuprofen, Metformin, Obesity, Type 2 diabetes, Zucker diabetic fatty rats
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