ABSTRACT
Betatrophin [also known as lipasin, angiopoietinlike 8 (ANGPTL8), refeeding induced in fat and liver (RIFL), or hepatocellular carcinomaassociated gene TD26], a 22kDa protein in the angiopoietinlike family, is a liverderived hormone that promotes pancreatic ßcell proliferation and lipid metabolism. The aim of the present study was to investigate the effect of recombinant betatrophin on ßcell regeneration in a neonatal streptozotocin (STZ)induced diabetic rat model. Onedayold Wistar rats were injected with STZ (100 mg/kg), followed by intraperitoneal administration of betatrophin to the STZinjected rats for 6 days. Plasma glucose and body weight were monitored. On days 4 and 7, expression levels of pancreatic duodenal homeobox gene1 (PDX1), the Bax/Bcell lymphoma2 (Bcl2) ratio and plasma insulin were assessed, and the ßcell proliferation rate was determined. Pancreatic islet area and number were determined at 10 weeks. It was found that betatrophin treatment alleviated STZinduced hyperglycemia, elevated pancreatic expression levels of Bcl2, PDX1, plasma insulin levels and the ßcell proliferation rate on days 4 and 7. Longterm betatrophin treatment improved glucose tolerance, associated with improved plasma insulin levels and ßcell mass. These results suggest that early administration of betatrophin promotes ßcell proliferation in STZinduced diabetic neonates and prevents the development of diabetes in adults.
Subject(s)
Angiopoietin-like Proteins/pharmacology , Diabetes Mellitus, Experimental , Hyperglycemia , Insulin-Secreting Cells , Angiopoietin-Like Protein 8 , Animals , Animals, Newborn , Cell Proliferation/drug effects , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/prevention & control , Homeodomain Proteins/biosynthesis , Hyperglycemia/chemically induced , Hyperglycemia/drug therapy , Hyperglycemia/metabolism , Hyperglycemia/pathology , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/pathology , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Rats , Rats, Wistar , Recombinant Proteins/pharmacology , Trans-Activators/biosynthesisABSTRACT
The present study was aimed to explore the effects of intraperitoneal injection of growth hormone releasing peptide-6 (GHRP-6), a ghrelin receptor agonist, on food intake and neuronal activity of feeding-related nuclei in the hypothalamus of NMRI mice. Accumulated amount of food intake was measured, and total number of c-fos immunoreactive neurons in arcuate nucleus (ARC), paraventricular nucleus (PVN) and supraoptic nucleus (SON) was counted by immunohistochemistry at 1, 3 and 6 h after the GHRP-6 injection. The results showed that GHRP-6 significantly increased the amount of food intake with a peak at 3 h after the GHRP-6 injection. Meanwhile, GHRP-6 could promote c-fos expression in the ARC and PVN independent of food intake, and the total number of c-fos immunoreactive neurons was peaked at 1 h after injection and then decreased gradually. These results suggest that GHRP-6 may increase food intake in time-dependent manner, which is associated with up-regulations of c-fos protein expression in the ARC and PVN.
Subject(s)
Arcuate Nucleus of Hypothalamus , Neurons , Animals , Eating , Immunohistochemistry , Male , Mice , Oligopeptides , Paraventricular Hypothalamic Nucleus , Proto-Oncogene Proteins c-fos , Receptors, Ghrelin , Supraoptic NucleusABSTRACT
Classical swine fever virus (CSFV) is an etiologic agent that causes a highly contagious disease in pigs. Laying a foundation to solve problems in its pathogenic mechanism, microarray analysis was performed to detect the gene transcriptional profiles in peripheral blood mononuclear cells (PBMC) following infection with a Chinese highly virulent CSFV strain Shimen. Three susceptible pigs were inoculated intramuscularly with a lethal dose (1.0x10(6) TCID(50)) of CSFV. Pigs showed classical CSF signs, depletion of lymphocytes and monocytes consistent with CSFV infection, and the CSFV genome was also confirmed in the PBMC. The PBMC were isolated at 1, 3, 6 and 9 days post-inoculation (dpi). Total RNA were extracted and subjected to microarray analysis. Data showed that expression of 847 genes wherein 467 genes were known function and the remaining 380 genes were unknown function, and 541 up- and 306 down-regulation, altered after infection. There were 54, 181, 438 and 354 up- and 61, 120, 218 and 145 down-regulated genes presented on 1, 3, 6 and 9dpi, respectively. These genes were involved in immune response (14.5%), apoptosis (3.3%), signal transduction (7.6%), transcription (4.4%), metabolism (11%), transport (3.9%), development (6.8%) and cell cycle (3.7%). Results demonstrated its usefulness in exploring the pathogenic mechanisms of CSFV.
