Proceedings for Annual Meeting of The Japanese Pharmacological Society
Online ISSN : 2435-4953
The 96th Annual Meeting of the Japanese Pharmacological Society
Session ID : 96_3-B-O06-6
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Oral Sessions
Focus on the diabetic brain: Upregulation of orexin receptor and plasma orexin level in obese diabetic rats
*Yuka KohdaNobuyuki FukuishiHitoshi Matsumura
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Abstract

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.

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