Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 7 No. 6 December 24, 2020 p.291-299
Original Article
Age-related hepatic glucose-dependent insulinotropic polypeptide expression is modified by ongoing thiamine supplementation in obese diabetic rats
  • Yuka Kohda (Department of Pharmacotherapeutics, Osaka University of Pharmaceutical Sciences /
Yuka Kohda
Department of Pharmacotherapeutics, Osaka University of Pharmaceutical Sciences
Keywords: Ongoing thiamine supplementation, Hepatic GIP expression, Glucose toxicity, Obesity, Aged obese diabetic rat

Obesity and type 2 diabetes mellitus have become worldwide epidemics. Evidence indicates that glucose-dependent insulinotropic polypeptide (GIP) secreted by the intestines may partially underlie these conditions, considering that GIP levels are associated with lipid deposition and fat mass expansion. However, recent studies have found that GIP is also present in other tissues, such as the liver. Notably, one study discovered through microarray analyses of livers from obese diabetic rats that the transcriptional modulation of GIP also occurred in the liver. Otsuka Long-Evans Tokushima Fatty (OLETF) rats were chosen for this experiment because previous studies have shown that thiamine (vitamin B1) could successfully decrease the tendency of the animal toward obesity and mitigate the complications of diabetes. Here, the rats were randomly assigned to either the control (non-supplemented) or thiamine-supplemented (2 g thiamine/L in drinking water) groups. For this investigation, unlike that for young rats, OLETF rats were chosen for the experimental period at 93 weeks of age. Ageing is also a risk factor for diabetes and its complications. In this study, hepatic GIP expression was analysed using western blotting, suggesting that GIP was present in the livers of both obese diabetic OLETF rats and obese diabetic rats that received ongoing thiamine supplementation. Results showed that hepatic GIP expression had occurred and that liver-derived GIP may exist. Moreover, results showed that ongoing thiamine supplementation modified the hepatic GIP expression and prevented additional weight gain and complications arising from obesity and diabetes.