Effect And Mechanism Of Tributyltin On Glucose Homeostasis In Male Mice

Organotin compounds cause multiple toxic effects on animals,but the mechanism by which tributyltin(TBT)induces diabetes has not been revealed.In this study,male KM mice were exposed at 0.5,5 and 50 ?g/kg concentration of TBT for 45 days,the results were shown as follow:1.After exposure for 45 days,the gain of body weight increased and reached a significant difference in the 50 ?g/kg group.The abdominal fat mass in the treated groups were all significantly elevated,showing a development of obesity.The fasting blood glucose level increased significantly in the 50 ?g/kg group.2.TBT exposure caused metabolic disorders,compared with the control group,serum c-peptide levels showed an increase trend.Fasting insulin levels were increased and reached a significant difference in the 50 ?g/kg group.The glucagon levels in mice were significantly decreased in a dose-dependent manner.The serum adiponectin levels in 0.5,5 and 50 ?g/kg increased significantly.3.After exposure for 45 days,the transcription of glucagon gene in the pancreas was dose-dependently down regulated.There was a significant difference in 5 ?g/kg and 50?g/kg groups compared to the control.While the transcription of insulin gene showed an up regulation and reached a significant difference in the 5 ?g/kg,50 ?g/kg groups.In addition,glucagon receptor gene transcription was down regulated after exposure,with a significant difference at the 0.5 ?g/kg group.4.The a-cell,?-cell relative area and both the cell mass were decreased.The apoptosis rate of the both cells in the 0.5 ?g/kg treatment showed a significant decrease.5.The levels of serum GLP-1 showed no significant change.The levels of GLP-1 amide were significantly increased in the 0.5 and 50 ?g/kg groups.But the pancreatic GLP-1R decreased and reached a significant difference in the 0.5 and 50 ?g/kg groups.In summary:exposure to TBT for 45 days caused obesity and hyperglycemia symptoms in male mice,accompanied with hyperinsulinemia and high serum adiponectin levels.The main reason for the increased serum insulin levels might be the up-regulation of insulin gene transcription.Meanwhile,TBT caused the reduction of ?-cell and ?-cell mass.TBT exposure causes glucagon gene down-regulation,which is one of the reasons for the decrease of serum glucagon levels.