Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 4 No. 6 December 21, 2017 p.279-284
Original Article
Hepatic glucose-dependent insulinotropic polypeptide expression is modified by supplementing high-dose thiamine in obese diabetic rats
  • Yuka Kohda (Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences /
Yuka Kohda , Akie Maekita , Takao Tanaka , Hitoshi Matsumura
Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences
Keywords: Thiamine supplementation, Hepatic GIP expression, Glycolipid toxicity, Obesity, Diabetic complications

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.