肥満を伴う糖尿病ラットにおける脳内オレキシン受容体発現と血漿中オレキシン濃度の増大

抄録

Diabetes mellitus and brain toxicity are closely linked. Oxidative stress, obesity, insulin resistance, and glucose toxicity can affect the brain. Orexin-A, also known as hypocretin-1, participates in many physiological processes through its activated receptor. Orexin-A has been associated with feeding behavior, obesity, and pathogenesis of Alzheimer's disease. We reported that high-dose thiamine in obese diabetic Otsuka Long–Evans Tokushima Fatty (OLETF) rats leads to reduced obesity and metabolic disorders. In addition, we found that plasma orexin-A levels in OLETF rats can be modulated by thiamine supplementation under conditions of oxidative stress. Herein, we focused on orexin-A in obese diabetic OLETF rats. At 58 weeks of age, the rats showed an increase in body weight and blood glucose levels. Plasma orexin-A was measured by ELISA and tended to be higher in obese diabetic OLETF rats than in non-obese diabetic control rats. We evaluated hypocretin receptor 1 (Hcrtr1, also orexin-A receptor) gene expression in the brain of diabetic OLETF rats by reverse transcription-polymerase chain reaction and found that diabetic OLETF rats exhibited higher orexin-A receptor gene expression in the brain than controls. The results presented here are expected to provide a better understanding of the role of orexin-A and its contribution to diabetic brain.