Hepatic glucose-dependent insulinotropic polypeptide expression is modified by supplementing high-dose thiamine in obese diabetic rats

Abstract

-Glucose toxicity and lipotoxicity are important states in obesity and diabetes. We previously reported that thiamine supplementation decreases body weight and visceral fat mass in rats with obesity-related diabetes. Glucose-dependent insulinotropic polypeptide (GIP) acts on pancreatic β cells to promote insulin secretion. According to established theory, GIP is derived from the gastrointestinal tract. We previously discovered increased expression of the GIP gene in the livers of obese rats with diabetes receiving high-dose thiamine. We referred to our previous dataset of gene expression analysis using a microarray for livers, which led to the new idea for the present study. We focused on "liver-derived GIP" to demonstrate GIP protein expression in the liver and visually present localization of GIP in the liver. Four-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were randomly divided into two groups: an unsupplemented control group and a thiamine-supplemented group receiving 2 g of thiamine/L in drinking water for 51 weeks. GIP protein expression in the livers of OLETF rats at 55 weeks of age were determined by western blotting and immunohistochemical analysis. GIP protein expression in the liver was increased in thiamine-supplemented rats compared with that in controls, suggesting that it is involved in preventing and controlling obesity-related diabetic complications. The novel findings of this study that GIP is expressed in the liver, is likely to be added to the story regarding GIP modification of the obese diabetic state.

Thiamine supplementation modulates oxidative stress by inhibiting hepatic adenosine diphosphate (ADP)-ribosylation in obese diabetic rats

“…Additionally, hepatic triglyceride accumulation was significantly reduced with high-dose thiamine supplementation (Tanaka et al, 2010;Kohda et al, 2012b). Moreover, we noted improvements in biochemical findings, degree of fatty liver, and obesity-related hepatic pathology and dysfunction (Tanaka et al, 2010;Kohda et al, 2012bKohda et al, , 2017. As a step forward, in the present study, we focused on protein modification, i.e., hepatic ADP-ribosylation that reflects PARP-1 activation and an increased oxidative stress condition.…”

“…Several of these genes were found to participate in carbohydrate metabolism, lipid metabolism, vascular physiology, and carcinogenesis (Tanaka et al, 2010;Kohda et al, 2012bKohda et al, , 2017. Although corroboration is necessary, our previous findings indicate that thiamine has the potential to prevent obesity and metabolic disorders in OLETF rats (Tanaka et al, 2010;Kohda et al, 2012bKohda et al, , 2017.…”

“…The transcript expression levels of genes, which were assessed using gene microarrays, indicated a difference in hepatic expression with high-dose thiamine supplementation (Tanaka et al, 2010;Kohda et al, 2012bKohda et al, , 2017. Several of these genes were found to participate in carbohydrate metabolism, lipid metabolism, vascular physiology, and carcinogenesis (Tanaka et al, 2010;Kohda et al, 2012bKohda et al, , 2017. Although corroboration is necessary, our previous findings indicate that thiamine has the potential to prevent obesity and metabolic disorders in OLETF rats (Tanaka et al, 2010;Kohda et al, 2012bKohda et al, , 2017.…”

“…We previously found that high-dose thiamine prevents obesity and diabetic complications in OLETF rats that exhibit progressive obesity and metabolic disorders (Tanaka et al, 2010;Kohda et al, 2012bKohda et al, , 2017. In this study, we additionally assessed Long-Evans Tokushima Otsuka (LETO) rats, which are the nondiabetic/lean counterparts of OLETF rats.…”

“…In OLETF rats, thiamine supplementation averted obesity, mainly through a reduction in visceral adiposity, and prevented metabolic disorders (Tanaka et al, 2010;Kohda et al, 2012b). The transcript expression levels of genes, which were assessed using gene microarrays, indicated a difference in hepatic expression with high-dose thiamine supplementation (Tanaka et al, 2010;Kohda et al, 2012bKohda et al, , 2017. Several of these genes were found to participate in carbohydrate metabolism, lipid metabolism, vascular physiology, and carcinogenesis (Tanaka et al, 2010;Kohda et al, 2012bKohda et al, , 2017.…”