ABSTRACT
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
Effect of the dipeptidyl peptidase-4 inhibitor linagliptin on structural manifestations of diabetic nephropathy was studied in BKS.Cg-Dock7m+/+Leprdb/J mice (experimental model of type 2 diabetes mellitus). Linagliptin (10 mg/kg per day) or vehicle was administered by gavage over 8 weeks. Mesangial expansion, thickening of the basement membrane in glomerular capillaries and proximal tubules, and retraction of cytopodia were less pronounced in mice receiving linagliptin. The protective effect of linagliptin on the kidney structure was not associated with its hypoglycemic action.
