Diabetic hyperglycemia is typically accompanied by various protein modifications, indicating hyperglycemic glucotoxicity. Overactivation of poly [adenosine diphosphate (ADP)-ribose] polymerase 1 (PARP-1) has been implicated in the pathogenesis of oxidative stress-related diseases including diabetes and its complications. Furthermore, obesity and diabetes are known to be associated with a substantial risk of chronic liver disease. We have previously reported that thiamine supplementation prevented obesity and diabetes-related liver disease. As a step forward, in the present study, we focus on hepatic ADP-ribosylation that reflects PARP-1 activation and an increased oxidative stress condition. Otsuka Long-Evans Tokushima Fatty (OLETF) rats were randomly divided into the following groups: thiamine-supplemented and unsupplemented control groups. The thiamine-supplemented group received 2 g of thiamine/L of drinking water for 33 weeks. ADP-ribosylated protein expression was analyzed in the livers of OLETF rats using Western blotting. Moreover, the fasting blood glucose level was measured in these rats. The obese diabetic OLETF rats exhibited high ADP-ribosylated protein expression in the liver. Interestingly, hepatic ADP-ribosylated protein expression and fasting blood glucose levels were lower in the thiamine-supplemented OLETF group than in the control OLETF group. These results suggest that thiamine supplementation attenuates oxidative stress by inhibiting hepatic ADP-ribosylation in OLETF rats. The beneficial effect of high-dose thiamine on oxidative stress-related diseases could be attributed to its inhibitory effect on PARP-1 activation, in addition to its role as a coenzyme. Furthermore, we found that thiamine supplementation prevented fasting hyperglycemia, suggesting that high-dose thiamine modifies the hepatic glucose metabolism and obesity-induced hepatic insulin resistance.
Overactivation of poly (ADP-ribose) polymerase-1 (PARP-1) has been implicated in the pathogenesis of oxidative stress-related diseases, including diabetes and its complications. Obesity is linked with type 2 diabetes. We previously reported that thiamine supplementation prevents obesity and diabetes-related liver disease. In this study, we focused on hepatic ADP-ribosylation, which reflects the activation of PARP-1. Obese diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats were randomly divided into two groups: a thiamine-supplemented group and an unsupplemented control group. ADP-ribosylated protein expression in the liver was determined by western blotting. Obese diabetic OLETF rats showed increased ADP-ribosylated protein expression in the liver. Hepatic ADP-ribosylated protein expression in thiamine-supplemented OLETF rats was lower than that in the unsupplemented control OLETF rats. These results suggest that thiamine supplementation modulates oxidative stress by inhibiting hepatic ADP-ribosylation in OLETF rats. The beneficial effect of high-dose thiamine on oxidative stress-related diseases may also be attributable to its inhibitory effect on PARP-1activation in addition to its role as a coenzyme.
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