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. 2022 Jan 31;17(1):e0263300.
doi: 10.1371/journal.pone.0263300. eCollection 2022.

d-allulose protects against diabetic nephropathy progression in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes

Misato Niibo  1   2 , Akane Kanasaki  1 , Tetsuo Iida  1 , Keisuke Ohnishi  2 , Taro Ozaki  2 , Kazuya Akimitsu  3 , Tetsuo Minamino  2
Affiliations

d-allulose protects against diabetic nephropathy progression in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes

Misato Niibo et al. PLoS One. .

Abstract

d-allulose is a rare sugar that has been reported to possess anti-hyperglycemic effects. In the present study, we hypothesized that d-allulose is effective in attenuating the progression of diabetic nephropathy in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model of type 2 diabetes mellitus. Drinking water with or without 3% d-allulose was administered to OLETF rats for 13 weeks. Long-Evans Tokushima Otsuka rats that received drinking water without d-allulose were used as non-diabetic control rats. d-allulose significantly attenuated the increase in blood glucose levels and progressive mesangial expansion in the glomerulus, which is regarded as a characteristic of diabetic nephropathy, in OLETF rats. d-allulose also attenuated the significant increases in renal IL-6 and tumor necrosis factor-α mRNA levels in OLETF rats, which is a proinflammatory parameter. Additionally, we showed that d-allulose suppresses mesangial matrix expansion, but its correlation with suppressing renal inflammation in OLETF rats should be investigated further. Collectively, our results support the hypothesis that d-allulose can prevent diabetic nephropathy in rats.

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Conflict of interest statement

The authors have read the journal’s policy and have the following competing interests: MN, AK, and TI are paid employees of Matsutani Chemical Industry Co., Ltd. D-Allulose is a marketed product of Matsutani Chemical Industry Co., Ltd. These do not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Periodic changes in the biochemical parameters relating glucose metabolism in OLETF and LETO rats.
(A) Non-fasting blood glucose. (B) Fasting blood glucose. (C) Non-fasting insulin levels. The data are presented as mean ± standard error (SE) (n = 10 for OLETF rats and n = 6 for LETO rats). The overall P value from the two-way repeated measures ANOVA with repeated measures is shown in the graph. abDifferent letters in the same column indicate statistical difference, P < 0.05, Tukey’s multiple comparison test. LETO, Long-Evans Tokushima Otsuka; OLETF, Otsuka Long-Evans Tokushima fatty; O-C, OLETF control; O-A, OLETF d-allulose.
Fig 2
Fig 2. Histological analyses of kidneys in LETO and OLETF rats.
(A) Kidney histological sections by the periodic acid-Schiff (PAS) stains (400 ×). (B) PAS-positive area within the total glomerular area. The data are presented as mean ± standard error (SE) (n = 10 for OLETF rats and n = 6 for LETO rats). abDifferent letters in the same column indicate statistical difference, P < 0.05, Tukey’s multiple comparison test. PAS, periodic acid-Schiff; LETO, Long-Evans Tokushima Otsuka; OLETF, Otsuka Long-Evans Tokushima fatty; O-C, OLETF control; O-A, OLETF d-allulose.
Fig 3
Fig 3. Effects of d-allulose on renal mRNA levels of proinflammatory cytokines.
(A) mRNA levels of interleukin-6 (IL-6). (B) mRNA levels of tumor necrosis factor-α (TNF-α). The data are presented as mean ± standard error (SE) (n = 10 for OLETF rats and n = 6 for LETO rats). abDifferent letters in the same column indicate statistical difference, P < 0.05, Tukey’s multiple comparison test. GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; LETO, Long-Evans Tokushima Otsuka; OLETF, Otsuka Long-Evans Tokushima fatty; O-C, OLETF control; O-A, OLETF d-allulose.
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