Investigation of d-allulose effects on high-sucrose diet-induced insulin resistance via hyperinsulinemic-euglycemic clamps in rats

Yukie Natsume; Takako Yamada; Tetsuo Iida; Nobuaki Ozaki; Yang Gou; Yoshiharu Oshida; Teruhiko Koike

doi:10.1016/j.heliyon.2021.e08013

Investigation of d-allulose effects on high-sucrose diet-induced insulin resistance via hyperinsulinemic-euglycemic clamps in rats

Heliyon. 2021 Sep 17;7(9):e08013. doi: 10.1016/j.heliyon.2021.e08013. eCollection 2021 Sep.

Authors

Yukie Natsume¹, Takako Yamada², Tetsuo Iida², Nobuaki Ozaki³, Yang Gou⁴, Yoshiharu Oshida⁵, Teruhiko Koike^{1

4}

Affiliations

¹ Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Aichi, Japan.
² Research and Development, Matsutani Chemical Industry Co., Ltd., Itami, Hyogo, Japan.
³ Division of Endocrinology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Aichi, Japan.
⁴ Department of Sports Medicine, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan.
⁵ Minami Seikyo Hospital, Nagoya, Aichi, Japan.

Abstract

d-Allulose, a C-3 epimer of d-fructose, is a rare sugar that has no calories. Although d-allulose has been reported to have several health benefits, such as anti-obesity and anti-diabetic effects, there have been no reports evaluating the effects of d-allulose on insulin resistance using a hyperinsulinemic-euglycemic clamp (HE-clamp). Therefore, we investigated the effects of d-allulose on a high-sucrose diet (HSD)-induced insulin resistance model. Wistar rats were randomly divided into three dietary groups: HSD containing 5% cellulose (HSC), 5% d-allulose (HSA), and a commercial diet. The insulin tolerance test (ITT) and HE-clamp were performed after administration of the diets for 4 and 7 weeks. After 7 weeks, the muscle and adipose tissues of rats were obtained to analyze Akt signaling via western blotting, and plasma adipocytokine levels were measured. ITT revealed that d-allulose ameliorated systemic insulin resistance. Furthermore, the results of the 2-step HE-clamp procedure indicated that d-allulose reversed systemic and muscular insulin resistance. d-Allulose reversed the insulin-induced suppression of Akt phosphorylation in the soleus muscle and epididymal fat tissues and reduced plasma TNF-α levels. This study is the first to show that d-allulose improves systemic and muscle insulin sensitivity in conscious rats.

Keywords: Epididymal fat; Hyperinsulinemic-euglycemic clamp; Insulin resistance; Rare sugar; Soleus muscle; d-allulose.