Laboratory of Morphometry, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Pancreas. 2011 Jul;40(5):715-22. doi: 10.1097/MPA.0b013e3182153922.
We sought to evaluate the effects of telmisartan, sitagliptin, or their combination on pancreatic ultrastructural alterations in high-fat-fed C57BL/6 mice.
Three-month-old C57BL/6 mice were fed with standard chow (SC, 10% lipids) or high-fat diet (HF, 60% lipids) during 10 weeks to induce obesity and its comorbidities. After this period, treatment began (lasted 6 weeks), and the HF group was divided into 4 subgroups: untreated HF, HF plus telmisartan (5 mg/kg per day), HF plus sitagliptin (1.1 g/kg per day), and HF plus telmisartan plus sitagliptin. Drugs were mixed with diet. Biochemical analyses, radioimmunoassay, immunofluorescence, stereology, and transmission electron microscopy were performed to assess pancreatic remodeling.
Overweight, hyperinsulinemia, hyperglycemia, and dyslipidemia were found in the HF group, but these outcomes were controlled by the different treatments. Untreated HF animals also showed alterations concerning distribution of α/β cell followed by large and numerous lipid droplets within pancreas. Telmisartan and sitagliptin as monotherapy alleviated these findings, and a complete reversal of pancreatic steatosis was observed after treating with the combination of the 2 drugs.
AT1 receptor blockade, partial peroxisome proliferator-activated receptor gamma activation, and extended incretin action emerge as feasible strategies to control pancreatic steatosis and avoid progression of pancreatic diseases due to lipotoxicity.
我们旨在评估替米沙坦、西他列汀或二者联合应用对高脂肪喂养 C57BL/6 小鼠胰腺超微结构改变的影响。
3 月龄 C57BL/6 小鼠在 10 周内分别用标准饲料（SC，10%脂肪）或高脂肪饲料（HF，60%脂肪）喂养，以诱导肥胖及其合并症。经过这段时间后，开始治疗（持续 6 周），HF 组被分为 4 个亚组：未治疗的 HF、HF 加替米沙坦（5mg/kg/天）、HF 加西他列汀（1.1g/kg/天）和 HF 加替米沙坦加西他列汀。药物与饮食混合。进行生化分析、放射免疫测定、免疫荧光、体视学和透射电子显微镜检查，以评估胰腺重塑。
HF 组出现超重、高胰岛素血症、高血糖和血脂异常，但这些结果通过不同的治疗得到了控制。未经治疗的 HF 动物还表现出α/β细胞分布改变，随后胰腺内出现大量脂质滴。替米沙坦和西他列汀单药治疗缓解了这些发现，联合应用这两种药物可完全逆转胰腺脂肪变性。
AT1 受体阻断、部分过氧化物酶体增殖物激活受体 γ 激活和延长肠促胰岛素作用可能是控制胰腺脂肪变性和避免脂毒性引起的胰腺疾病进展的可行策略。
