Alteration of Sweet and Bitter Taste Sensitivity with Development of Glucose Intolerance in Non-insulin-Dependent Diabetes Mellitus Model OLETF Rats

Abstract

Patients with diabetes exhibit altered taste sensitivity, but its details have not been clarified yet. Here, we examined alteration of sweet taste sensitivity with development of glucose intolerance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats as a model of non-insulin-dependent diabetes mellitus. Compared to the cases of Long Evans Tokushima Otsuka (LETO) rats as a control, glucose tolerance of OLETF rats decreased with aging, resulting in development of diabetes at 36-weeks-old. In brief-access tests with a mixture of sucrose and quinine hydrochloride, OLETF rats at 25 or more-weeks-old seemed to exhibit lower sweet taste sensitivity than age-matched LETO ones, but the lick ratios of LETO, but not OLETF, rats for the mixture and quinine hydrochloride solutions decreased and increased, respectively, aging-dependently. Expression of sweet taste receptors, T1R2 and T1R3, in circumvallate papillae (CP) was almost the same in LETO and OLETF rats at 10-and 40-weeks-old, while expression levels of a bitter taste receptor, T2R16, were greater in 40-weeks-old rats than in 10-weeks-old ones in both strains. There was no apparent morphological alteration in taste buds in CP between 10-and 40-weeks-old LETO and OLETF rats. Metagenomic analysis of gut microbiota revealed strain-and aging-dependent alteration of mucus layer-regulatory microbiota. Collectively, we concluded that the apparent higher sweet taste sensitivity in 25 or more-weeks-old OLETF rats than in age-matched LETO rats was due to the aging-dependent increase of bitter taste sensitivity in LETO rats with alteration of the gut microbiota.