Function And Glucose Metabolism Study In Rat Pancreatic α β Cell Apoptosis Induced Hyperuricemia

Objective:To observe the effect on islet a cells in the dysglycemia rats induced by hyperuricemia.Methods:66Wista rats were divided into three groups:hyperuricemia groups (HUA), normal control groups (NC) and diabetes mellitus groups (DM). To establish the dysglycemia rats induced by hyperuricemia with high yeast feed, adenine and oteracil potassium. The diabetes mellitus model was established by intraperitoneal injection of STZ after12weeks high-glucose and high-fat feeding. Measuring serum uric acid (UA), fasting blood glucose (FBG), with angular vein blood and caudal vein blood every two weeks. The levels of fasting insulin (FINS) and glucagons were detected by ELISA. Serial paraffin-embedded sectioning with double staining in islet of pancreas and hematoxylin/eosin staining were applied to observe the anatomic structure of the pancreas, the morphology, quantity and distribution of the islets in rats.Results:In HUA groups, from the4th week, the level of uric acid and fasting glucose, was showing a trend of continuous dynamic rise, compared with the zero-week group,(P0.01). In HUA groups, from the4th week, the standard of fasting serum insulin was increased, increased significantly while in the8-12weeks, reduced to baseline at16weeks, compared with the zero-week group, the difference was statistically significant (P <0.01). Compared with the zero-week group, the level of fasting serum glucagon did not change significantly, in0-12weeks, while at16weeks decreased significantly (P<0.01). Compare with the NC groups, the shape of the islet in HUA groups became irregular and the number of islet decreased obviously, the distribution proportion reduced significantly. But the number of islet in HUA groups was increased obviousely, when compared with those in DM group. At16weeks, the HUA groups compared with the NC groups, the proportion and distribution of pancreatic a cells,(3cell were no significant change (P>0.05), different time periods without dynamic change (P>0.05) in the HUA group.Conclusions:Changes in pancreatic a-cell function may have no associated with the dysglycemia induced by hyperuricemia, in rats. Objective:To investigate the effect of the C-jun N-terminal kinase (JNK) pathway and cell apoptosis of islet β-cells in the dysglycemia rats induced by hyperuricemia.Methods:The apoptotic beta-cell in islets were detected and quantified by the TUNEL technology (labeling of DNA strand breaks). Exam and half-quantify the apoptosis related protein (JNK、c-Jun、c-Fos、ATF-2、Jun-D) by immunocytochemical staining.Results:In HUA groups, from the4th week, the frequency of P-cell apoptosis, was showing a trend of continuous dynamic rise, compared with the zero-week group,(P <0.01).In HUA groups at16th week compared with the NC group, islet cell apoptosis was significantly increased(P<0.01). In HUA groups compared with the zero-week group, from the4th week, the mean density of JNK, ATF-2and Jun-D began to raise. The means density of JNK in HUA groups continues to rise until the8-th week (P<0.05), ATF-2, Jun-D continues to rise until the12-th week (P<0.05). The immunohistochemistry results shows that in0-16weeks of HUA groups, the expression of the JNK and Jun-D were in the cytoplasm. At the4th week, the ATF-2in HUA groups were in the nucleus and the cytoplasm, other time periods were in the cytoplasm. The c-Jun and c-Fos expressions in HUA groups and NC groups were negative (P>0.05)Conclusions:The frequency of β-cell apoptosis in the dysglycemia rats induced by hyperuricemia was increased. At the early and mid-stage of the experiment, the apoptosis of beta cell may has correlation with the JNK non-dependent transcriptional pathway. At the later stages, the apoptosis of the beta cell mechanism is unclear.