Objective:To investigate the anti-diabetic effect of the root extract of Annona muricata(AME)in streptozotocin-nicotinamide-induced type 2 diabetic(T2DM)mice.Methods:After 4 weeks of high-fat diet,ICR mice were given ...Objective:To investigate the anti-diabetic effect of the root extract of Annona muricata(AME)in streptozotocin-nicotinamide-induced type 2 diabetic(T2DM)mice.Methods:After 4 weeks of high-fat diet,ICR mice were given 1 g/kg nicotine and 120 mg/kg streptozotocin(STZ)orally to construct a T2DM model.The T2DM mice were randomly divided into five groups:model group,200 mg/kg metformin group and 50,100,200 mg/kg AME groups.Drugs were oral administered continuously for 4 weeks.Fasting blood glucose and body weight were measured weekly.Oral glucose tolerance test(OGTT)and detection of serum glycated hemoglobin(HbA1c)level were performed one week before the end of the experiment.At the end of drug administration,serum total cholesterol(TG),triglycerides(TC),low-density lipoprotein levels(LDL-C)and insulin levels were tested by lipid detection kits;homeostasis model assessment-estimated insulin resistance(HOMA-IR)and HOMA-βindexes were calculated.Liver and kidney tissues were weighed to calculate organ indices and pathological tests were performed.Western blot was performed in the liver to detect adenosine monophosphate-activated protein kinase(AMPK),acetyl coenzyme A carboxylase(ACC),glucose-6-phosphate carboxylase(G6Pase),and phosphoenolpyruvate carboxykinase(PCK1)protein expression.Results:with 200 mg/kg AME significantly reduced fasting blood glucose,HbA1c,TG and LDL-C levels,protected liver and kindey in diabetic mice,decreased the area under the OGTT curve,inhibited ACC and G6Pase protein expressions,and activated AMPK protein expression.Conclusion:AME showed good therapeutic activity against T2DM,and the mechanism may be related to the activation of AMPK and inhibition of ACC and G6Pase proteins.展开更多
We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcri...We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcriptional regulation via phosphorylation of the C-terminal domain of RNA polymerase Ⅱ. The cyclin L2 protein contains an N-terminal "cyclin box" and C-terminal dipeptide repeats of alternating arginines and serines, a hallmark of the SR family of splicing factors. A new isoform and the mouse homologue of human cyclin L2 have also been cloned in this study. Human cyclin L2 is expressed ubiquitously in normal human tissues and tumor cells. We show here that cyclin L2 co-localizes with splicing factors SC-35 and 9G8 within nuclear speckles and that it associates with hyperphosphorylated, but not hypophosphorylated, RNA polymerase Ⅱ and CDK p110 PITSLRE kinase via its N-terminal cyclin domains. It can also associate with the SC-35 and 9G8 through its RS repeat region. Recombinant cyclin L2 protein can stimulate in vitro mRNA splicing. Overexpression of human cyclin L2 suppresses the growth of human hepatocellular carcinoma SMMC 7721 cells both in vitro and in vivo, inducing cellular apoptosis. This process involves up-regulation of p53 and Bax and decreased expression of Bcl-2. The data suggest that cyclin L2 represents a new member of the cyclin family, which might regulate the transcription and RNA processing of certain apoptosis-related factors, resulting in tumor cell growth inhibition and apoptosis.展开更多
基金National Natural Science Foundation of China(No.81460591)Hainan Medical University Training Fund(HY2018-09)。
文摘Objective:To investigate the anti-diabetic effect of the root extract of Annona muricata(AME)in streptozotocin-nicotinamide-induced type 2 diabetic(T2DM)mice.Methods:After 4 weeks of high-fat diet,ICR mice were given 1 g/kg nicotine and 120 mg/kg streptozotocin(STZ)orally to construct a T2DM model.The T2DM mice were randomly divided into five groups:model group,200 mg/kg metformin group and 50,100,200 mg/kg AME groups.Drugs were oral administered continuously for 4 weeks.Fasting blood glucose and body weight were measured weekly.Oral glucose tolerance test(OGTT)and detection of serum glycated hemoglobin(HbA1c)level were performed one week before the end of the experiment.At the end of drug administration,serum total cholesterol(TG),triglycerides(TC),low-density lipoprotein levels(LDL-C)and insulin levels were tested by lipid detection kits;homeostasis model assessment-estimated insulin resistance(HOMA-IR)and HOMA-βindexes were calculated.Liver and kidney tissues were weighed to calculate organ indices and pathological tests were performed.Western blot was performed in the liver to detect adenosine monophosphate-activated protein kinase(AMPK),acetyl coenzyme A carboxylase(ACC),glucose-6-phosphate carboxylase(G6Pase),and phosphoenolpyruvate carboxykinase(PCK1)protein expression.Results:with 200 mg/kg AME significantly reduced fasting blood glucose,HbA1c,TG and LDL-C levels,protected liver and kindey in diabetic mice,decreased the area under the OGTT curve,inhibited ACC and G6Pase protein expressions,and activated AMPK protein expression.Conclusion:AME showed good therapeutic activity against T2DM,and the mechanism may be related to the activation of AMPK and inhibition of ACC and G6Pase proteins.
文摘We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcriptional regulation via phosphorylation of the C-terminal domain of RNA polymerase Ⅱ. The cyclin L2 protein contains an N-terminal "cyclin box" and C-terminal dipeptide repeats of alternating arginines and serines, a hallmark of the SR family of splicing factors. A new isoform and the mouse homologue of human cyclin L2 have also been cloned in this study. Human cyclin L2 is expressed ubiquitously in normal human tissues and tumor cells. We show here that cyclin L2 co-localizes with splicing factors SC-35 and 9G8 within nuclear speckles and that it associates with hyperphosphorylated, but not hypophosphorylated, RNA polymerase Ⅱ and CDK p110 PITSLRE kinase via its N-terminal cyclin domains. It can also associate with the SC-35 and 9G8 through its RS repeat region. Recombinant cyclin L2 protein can stimulate in vitro mRNA splicing. Overexpression of human cyclin L2 suppresses the growth of human hepatocellular carcinoma SMMC 7721 cells both in vitro and in vivo, inducing cellular apoptosis. This process involves up-regulation of p53 and Bax and decreased expression of Bcl-2. The data suggest that cyclin L2 represents a new member of the cyclin family, which might regulate the transcription and RNA processing of certain apoptosis-related factors, resulting in tumor cell growth inhibition and apoptosis.
