#43732 - [node:field-team-member:0:field-contact-name:family], [node:field-team-member:0:field-contact-name:given] - [node:field-team-member:0:field-address:administrative-area] / [node:field-team-member:1:field-contact-name:family], [node:field-team-memb
As PPAR alpha agonists are clinically used to treat dyslipidemia in obesity, PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/24141786 - https://www.ncbi.nlm.nih.gov/pubmed/24141786 metabolic syndrome and type 2 diabetes individuals. PPAR alpha is expressed in pancreatic islets, and its agonist has been reported to improve pancreatic beta cell function in insulin-resistant rodents . However, other studies showed that PPAR alpha agonists produced a decrease in glucose-stimulated insulin secretion in beta cells. Thus it remains unclear whether long term use of PPAR alpha agonist in pre-diabetic or diabetic animal models is benefit to beta cell function or not, although PPAR alpha has both direct and indirect effects on the islet including the modulation of systemic insulin sensitivity [24,25]. The initial objective of this study was to observe the effect of PPAR alpha agonist on lipid metabolism as well as insulin resistance in obese MSG rats. The effects of fenofibrate on lipid levels at the dose of 100 mg per day for 4 weeks were also assessed. Fenofibrate therapylowered triglycerides and LDL-C level as well as HDL-C as shown in Figure 2D. These results showed some variance to that from clinical data in humans. Many researches have confirmed that in rodents fibrates may decrease HDL-C as a result of both decreased expression of HDL apolipoproteins, Vistusertib - http://hotweb.gepunet.com/comment/html/?28662.html apoA-I and apoA-II and the metabolism enzymes such as hepatic lipase [26-28]. But in humans fibrates have a positive effect on HDL cholesterol as well as on apoA-I and apoA-II concentrations. This different regulatory effects seems to be caused by differences apoA-I gene promoter in the two species [29,30]. We found that the fasting plasma insulin level showed a notable reduction after fenofibrate treatment as shown in Figure 1H. And we have also found the similar results in the normal Wistar rats treated with fenofibrate for 4 weeks. It is well established that plasma insulin level is decreased due to improved insulin sensitivity in tissues (the liver and muscle, two major targets of insulin action) in obesity and Type 2 diabetes. However, our results showed that fenofibrate did not improve insulin sensitivity in obese MSG rats. Thus we wondered how plasma insulin level was decreased and speculated that insulin secretion may be impaired in obese MSG rats after fenofibrate treatment. To PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28452055 - https://www.ncbi.nlm.nih.gov/pubmed/28452055 test our hypothesis, we measured insulin secretion in vivo with the hyperglycemic clamp which allowed for the quantitation ofLiu et al. Journal of Translational Medicine 2011, 9:176 http://www.translational-medicine.com/content/9/1/Page 8 ofFigure 5 Fenofibrate upregulates NF- kappaB and iNOS expression in the pancreas in obese MSG rats. Quantitative RT-PCR analysis of pancreatic NF- kappaB and iNOS mRNA levels (A), UCP2 and PPAR alpha mRNA levels (B) in the three groups. A comparative threshold cycle (CT) method was used for relative quantification of gene expression using b-actin for normalization. Measurements were carried out in triplicate for each sample. (C) Western blot analysis of pancreatic NF- kappaB p65, iNOS and TNF alpha protein levels in three groups. Beta actin served as loading control. Data represented the mean of at least three independent experiments ?s.e.m. *p < 0.05, ** p < 0.01 vs. control.pancreatic insulin release in response to a defined hyperglycemic stimulus. The hyperglycemic clamp has been demonstrated to be a reliable technique to evaluate insulin secretory function. The results in Figure 3 demonstrated that fenofibrate treated obese MSG rats exhibited impaired insulin release in.