ABSTRACT
We studied the relationships between body composition parameters and plasma levels of pancreatic, gut, and adipose tissue hormones regulating energy balance and glucose metabolism in diabetic db/db mice (BKS.Cg-Dock7m+/+Leprdb/J). The body composition parameters in mice aged 8, 12, and 16 weeks were assessed by magnetic resonance imaging. The concentrations of insulin, glucagon, ghrelin, glucagon-like peptide-1, glucose-dependent immunotropic peptide, leptin, resistin, and plasminogen activator-1 were measured by multiplex analysis at the age of 8 and 16 weeks. In comparison with non-diabetic control (db/+), db/db mice demonstrated high fat mass and reduced lean body mass and water content. In 8- and 16-week-old db/db mice, the levels of leptin (p<0.001), insulin (p<0.01), and glucagon-like peptide-1 (p<0.05) were elevated and the concentration of ghrelin (p<0.05) was reduced. The body weight and fat mass positively correlated with the levels of leptin, insulin, plasminogen activator-1, and glucagon-like peptide-1 and negatively correlated with ghrelin concentration. The results provide further details for characteristics of db/db mice, a widely used model of obesity and type 2 diabetes mellitus.
Subject(s)
Adipose Tissue/metabolism , Body Composition/physiology , Diabetes Mellitus, Type 2/blood , Gastrointestinal Hormones/blood , Pancreatic Hormones/blood , Animals , Ghrelin/blood , Glucagon/blood , Glucagon-Like Peptide 1/blood , Glucose/metabolism , Insulin/blood , Leptin/blood , Male , Mice , Mice, Inbred NOD , Plasminogen Activators/blood , Resistin/bloodABSTRACT
We studied the effects of dipeptidyl peptidase 4 (DPP4) inhibitor linagliptin on the expression of apoptosis regulator proteins Bcl-2 and Bad in the liver of db/db mice with genetically determined obesity and type 2 diabetes mellitus. The mice received daily linagliptin or saline (placebo) by gavage from week 10 to week 18 of life. In the liver of non-treated mice, the area positively stained for Bad was greater than the area of Bcl-2 expression, which created the conditions for apoptosis activation in liver at this age. Administration of linagliptin decreased Bad stained area and increased Bcl-2 stained area in the liver cells. At the same time, Bad stained area remained larger in treated mice than the area of Bcl-2 expression area, which attested to partial normalization of pro- and antiapoptotic protein balance.
Subject(s)
Linagliptin/therapeutic use , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Animals , Apoptosis/drug effects , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Liver , Male , Mice , Obesity/drug therapy , Obesity/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , bcl-Associated Death Protein/metabolismABSTRACT
We studied the effects of a melatonin-aluminum oxide-polymethylsiloxane complex (complex M) on the expression of apoptosis regulators Bcl-2 and Bad in the liver of homozygous db/db BKS.Cg-Dock7m+/+Leprdb/J mice with obesity and type 2 diabetes. Complex M or placebo was administered daily through the gastric tube during weeks 8-16 of life. In mice with type 2 diabetes mellitus receiving placebo, enhanced immunohistochemical reactions for proapoptotic Bad protein and weak response for anti-apoptotic Bcl-2 protein were observed. Administration of complex M shifted the ratio of apoptosis regulators: the area of Bcl-2 expression significantly increased and against the background of reduced Bad expression area. These findings attest to antiapoptotic effect of complex M in the liver on the model of type 2 diabetes mellitus.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hepatocytes/drug effects , Liver/drug effects , Melatonin/pharmacology , Obesity/drug therapy , Protective Agents/pharmacology , Aluminum Oxide/chemistry , Animals , Apoptosis/drug effects , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Disease Models, Animal , Female , Gene Expression Regulation , Hepatocytes/metabolism , Hepatocytes/pathology , Homozygote , Liver/metabolism , Liver/pathology , Melatonin/chemistry , Mice , Mice, Transgenic , Obesity/genetics , Obesity/metabolism , Obesity/pathology , Protective Agents/chemistry , Proto-Oncogene Proteins c-bcl-2/agonists , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Silicones/chemistry , bcl-Associated Death Protein/antagonists & inhibitors , bcl-Associated Death Protein/genetics , bcl-Associated Death Protein/metabolismABSTRACT
Toxicity of different types of manganese nanoparticles against glioblastoma U-87MG and U-251 cells and normal human cells was studied using MTT test. The selectivity of the toxic effect of nanoparticles was evaluated as the ratio of 50% cytotoxic concentration (СС50) for human embryos fibroblasts (FECh-15) to their СС50 for tumor cells. Five of 6 samples of tested nanoparticles demonstrated selective toxic effect in vitro. Manganese oxide nanoparticles were characterized by maximum selectivity (СС50 6.9 nM and 2.1 nM for U-87MG and U-251 cells, respectively): selectivity index for glioblastoma U-87MG and U-251 cells was 29 and 95.2, respectively. Manganese oxide nanoparticles used for MRI detection of gliomas can be used for designing an oncolytic agent for the treatment of glial tumors in humans.
Subject(s)
Glioblastoma/metabolism , Manganese/chemistry , Manganese/pharmacology , Nanoparticles/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Glioma/diagnostic imaging , Humans , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Oxides/chemistry , Oxides/pharmacologyABSTRACT
We studied the effect 24-h illumination on quantitative and qualitative parameters of the bone marrow cells in Wistar rats. It was shown that desynchronosis reduced the release of nucleated cells from the femoral bone, while melatonin weakened this effect. The number of bone marrow mesenchymal stromal cells was resistant to circadian rhythm disturbances, while proliferation depended on glucose concentration in the medium.
