Effects Of Pentamethylquercetin And Sleeve Gastrectomy In Neonatally Streptozotocin-induced Diabetic Rats

Type 2 diabetes mellitus (T2DM) has become one of the most common metabolic disorders during the past few decades. T2DM is characterized by the progression of diminishing insulin sensitivity and impaired pancreatic function. Although substantial amounts of anti-diabetic agents have been developed to tackle the disease, many patients still cannot achieve satisfactory glycaemic goals. Therefore, searching for alternative protective strategies is consequently of great interest.There have been growing interests in the application of natural components as antidiabetic agents during recent years. Pentamethylquercetin (PMQ), which is present in seabuckthorn (Hippophae rhamnoides), is a typical member of the polymethoxylated flavones (PMF) family. Previous studies have demonstrated that PMQ possesses many health beneficial effects including anti-carcinogenic and cardioprotective properties; however, its influence on glucose homeostasis has not been studied up until now.Sleeve gastrectomy (SG) has been validated as one of the restrictive surgical procedures to treat morbid obesity. Nowadays, accumulated evidence has demonstrated that SG-induced body weight loss is accompanied by improvement or resolution of type 2 diabetes mellitus and obesity-associated disorders including dyslipidemia, steatohepatitis and insulin resistance.Therefore, the present study was designed to investigate whether PMQ and SG could ameliorate hyperglycaemia in neonatally STZ-induced diabetic rat model. PartⅠ: Establishment of the neonatally STZ-induced diabetic rat modelObjective:To establish a diabetic rat model as the platform for the subsequent studies. Methods:Healthy Sprague-Dawley rats were obtained from the Center of Experimental Animals (Tongji Medical College, Huazhong University of Science and Technology, China) and kept for breeding. Male rat pups, aged 48h±2h, received STZ (Sigma, USA) administration intraperitoneally at a dose of 90mg/kg body weight. Normal rat pups received vehicle administration with the same volume. Fasting and fed blood biochemical parameters of the rats, including blood glucose, triglyceride, cholesterol and insulin levels, were monitored periodically at 6,8,10,12,14 and 16 weeks of age. Body weights were also followed during the study period. Results: n-STZ diabetic rats exhibited significantly elevated blood fed glucose and triglyceride levels, whereas fasting triglyceride, fasting and fed cholesterol levels remained close to normal. Furthermore, there was a progressive deterioration of diabetes in n-STZ diabetic rats as fasting glucose levels progressively increased. Body weights of the n-STZ diabetic rats were significantly reduced in comparison to normal rats. Conclusion:Neonatal injection of STZ into rats results in an ideal type 2 diabetic rat model. PartⅡ: Anti-diabetic effects of PMQ in neonatally STZ-induced diabetic rat modelObjective:To study the effects of PMQ in neonatally STZ-induced diabetic rats. Methods:The rats were randomly divided into the following groups (n=9-12): Control group (Nondiabetic rats); Diabetic group (Diabetic rats); PMQ intervened groups (Diabetic rats given PMQ at doses of 2.5,5,10,20 mg/kg). PMQ of all doses were given orally (once a day) by the gavage syringe at 8:30 a.m. when the rats were 6 weeks of age and continued for 10 consecutive weeks. Body weights were followed. Fasting and fed glucose, triglyceride (TG) and insulin levels were measured periodically at the 6th and 10th week after PMQ treatment. At the end of the study, oral glucose tolerance test (OGTT) was performed, and liver and pancreas were excised and weighed to obtain the organ indices. Results:PMQ intervention dose-dependently reduced postprandial glucose and triglyceride levels, prevented the onset of overt diabetes, ameliorated polydipsia symptom induced by diabetes, attenuated glucose intolerance, enhanced insulin sensitivity indices and decreased blood alanine aminotransferase (ALT) levels of n-STZ diabetic rats in comparison to their diabetic counterparts. Conclusion:PMQ exhibits great potential as an antidiabetic agent by improving glucose homeostasis. PartⅢ: Effects of sleeve gastrectomy in neonatally STZ-induced diabetic rat modelObjective:To study the effects of sleeve gastrectomy in neonatally STZ-induced diabetic rats. Methods:A total of 12 n-STZ diabetic rats were randomized into sleeve operation group (SLG, n=6) and sham operation group (SOG, n=6) when 12 weeks old. Randomly chosen normal rats made up of the normal control group (NC, n=6). Body weights were measured weekly. Daily intakes of water and food were followed for eight consecutive weeks postoperatively. Blood glucose levels were determined periodically at the 4th and 8th week after surgery. Insulin, ghrelin, Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels were assayed at the end of the study. Results:SLG rats demonstrated significantly lower body weight gain, reduced food and water intakes postoperatively when compared with their sham-operation counterparts. Nevertheless, resolution of diabetes was not observed in our study. Furthermore, there were no significant differences in glucose metabolism-associated hormones between SOG rats and SLG rats, including insulin GLP-1 and GIP. However, ghrelin level significantly decreased (P<0.01) in SLG group (58.01±3.75 pg/ml) after SG surgery compared to SOG group (76.36±3.51 pg/ml). Conclusion:SG was efficacious in controlling body weight. However, SG did not achieve improvement of diabetes in n-STZ diabetic rats.