ABSTRACT
Glucagon-like peptide-1 (GLP-1) is a potent glucoincretin hormone and an important agent for the treatment of type 2 diabetes. Here we demonstrate that B-cell translocation gene 2 (BTG2) is a crucial regulator in GLP-1-induced insulin gene expression and insulin secretion via upregulation of pancreatic duodenal homeobox-1 (PDX-1) in pancreatic beta-cells. GLP-1 treatment significantly increased BTG2, PDX-1 and insulin gene expression in pancreatic beta-cells. Notably, adenovirus-mediated overexpression of BTG2 significantly elevated insulin secretion, as well as insulin and PDX-1 gene expression. Physical interaction studies showed that BTG2 is associated with increased PDX-1 occupancy on the insulin gene promoter via a direct interaction with PDX-1. Exendin-4 (Ex-4), a GLP-1 agonist, and GLP-1 in pancreatic beta-cells increased insulin secretion through the BTG2-PDX-1-insulin pathway, which was blocked by endogenous BTG2 knockdown using a BTG2 small interfering RNA knockdown system. Finally, we revealed that Ex-4 and GLP-1 significantly elevated insulin secretion via upregulation of the BTG2-PDX-1 axis in pancreatic islets, and this phenomenon was abolished by endogenous BTG2 knockdown. Collectively, our current study provides a novel molecular mechanism by which GLP-1 positively regulates insulin gene expression via BTG2, suggesting that BTG2 has a key function in insulin secretion in pancreatic beta-cells.
Subject(s)
Animals , Humans , Male , Mice , Rats , Gene Expression Regulation/drug effects , Glucagon-Like Peptide 1/pharmacology , Homeodomain Proteins/genetics , Immediate-Early Proteins/genetics , Insulin/genetics , Insulin-Secreting Cells/drug effects , Mice, Inbred C57BL , Peptides/pharmacology , Promoter Regions, Genetic/genetics , Protein Binding/drug effects , Trans-Activators/genetics , Tumor Suppressor Proteins/genetics , Venoms/pharmacologyABSTRACT
PURPOSE: This study is to examine the relationship between clinical manifestations and MRI findings of children with CNS symptoms and signs. METHODS: A total of 447 inpatients with CNS symptoms and signs took brain MRI's at the Department of Pediatrics of Chungnam National University Hospital from July 2001 to June 2004. The results were retrospectively evaluated in terms of age, gender, chief complaints, and the findings of MRI and EEG based on the medical records. RESULTS: The overall incidence of abnormal MRI findings was 30.4%, of whom 44.7% were aged from one month to one year. The MRI findings were markedly different between under and over 6 years olds. In the former group, hydrocephalus, periventricular leukomalacia and hemorrhage were common while vascular malformation and brain tumor were more common in the latter group. Periventricular leukomalacia and hydrocephalus were shown to be the most frequent abnormal findings. 42.9% of those with seizures had abnormal MRI findings. Headache was common with 10.5% low incidence rate of abnormalies in MRI. The EEG findings were normal in 33.9% of the patients and there were not any articular correlations between EEG and MRI findings. CONCLUSION: MRI is important in the diagnosis of neurological disorders. However, caution should be taken in selecting patients since the MRI findings were normal in 69.6 % of the children with CNS symptoms and signs. This is the reason why more detailed standards of MRI for CNS manifestations are required.
Subject(s)
Child , Humans , Infant, Newborn , Brain Neoplasms , Brain , Diagnosis , Electroencephalography , Headache , Hemorrhage , Hydrocephalus , Incidence , Inpatients , Leukomalacia, Periventricular , Magnetic Resonance Imaging , Medical Records , Nervous System Diseases , Pediatrics , Retrospective Studies , Seizures , Vascular MalformationsABSTRACT
BACKGROUND: Reasons for obesity include environmental factors and, more largely so, genetic factors. There have been many studies on these genetic factors. So far, genes related to obesity such as Leptin, Uncoupling Protein(UCP), Peroxisome proliferator activated receptor-gamma(PPAR-gamma), and Beta3-adrener-gic receptor(beta3-AR) gene have been discovered. Among these, beta3-AR is expressed in visceral adipose tissue and is thought to contribute to the regulation of resting metabolic rate and lipolysis. The missense mutation of beta3-AR gene, resulting in replacement of tryptophan by arginine at position 64(Trp64Arg), is associated with decreased resting metabolic rate and weightgain. We performed this study to determine if Trp64Arg polymorphism of beta3-AR gene is associatedwith obesity in Koreans. METHOD: We investigated the relationship between the beta3-AR gene mutation and body mass index (BMI), waist circumference, hip circumference, waist to hip ratio(WHR), area of subcutaneous fat, area of visceral fat, visceral to subcutaneous fat ratio(VSR), and lipid profile. 198 subjects were included in this study of which 97 were of normal weight and 101 were obese. Anthropometric data was obtained from physical examination and medical records. RESULT: In the cases of beta3-AR gene mutation of the obese group, the ratio of Trp/Arg and Arg/Arg are 43% and 5%, respectively, which were higher than the normal group(36%, 1%), although a statistical significant was not found. There was significant difference in the are of subcutaneous fat. Normal group(Trp/Trp) measured at 213.9+/-109.6cm2 versus 244.0+/-127.7cm2 (Trp/Arg) and 323.9+/-189.9cm2(Arg/Arg) for the mutation groups. Circumference of waist, circumference of hip, WHR, area of visceral fat, and VSR were higher in the mutation groups than in normal subject, but not significantly different. CONCLUSION: These results suggest that a genetic mutation in the beta3-AR gene can affect body fat composition, and is associated with obesity in Korean adults.