Red rice koji extract alleviates hyperglycemia by increasing glucose uptake and glucose transporter type 4 levels in skeletal muscle in two diabetic mouse models

Takakazu Yagi; Koji Ataka; Kai-Chun Cheng; Hajime Suzuki; Keizaburo Ogata; Yumiko Yoshizaki; Kazunori Takamine; Ikuo Kato; Shouichi Miyawaki; Akio Inui; Akihiro Asakawa

doi:10.29219/fnr.v64.4226

Red rice koji extract alleviates hyperglycemia by increasing glucose uptake and glucose transporter type 4 levels in skeletal muscle in two diabetic mouse models

Food Nutr Res. 2020 Oct 8:64. doi: 10.29219/fnr.v64.4226. eCollection 2020.

Authors

Takakazu Yagi^{1

2}, Koji Ataka³, Kai-Chun Cheng^{3

4}, Hajime Suzuki⁵, Keizaburo Ogata⁶, Yumiko Yoshizaki⁷, Kazunori Takamine⁷, Ikuo Kato⁸, Shouichi Miyawaki², Akio Inui³, Akihiro Asakawa⁹

Affiliations

¹ Department of Oral Health, Kobe-Tokiwa Junior College, Kobe, Japan.
² Department of Orthodontics and Dentofacial Orthopedics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
³ Department of Pharmacological Sciences of Herbal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
⁴ Department of Medical Research, Chi-Mei Medical Center, Tainan City, Taiwan.
⁵ Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
⁶ Kitasato University Hospital, Sagamihara, Japan.
⁷ Division of Shochu Fermentation Technology, Education and Research Center for Fermentation Studies, Faculty of Agriculture, Kagoshima University, Kagoshima, Japan.
⁸ Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan.
⁹ Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

Abstract

Background: Red rice koji (RRK), prepared by growing Monascus species on steamed rice, has been reported to lower blood glucose levels in diabetic animal models. However, the action mechanism is not yet completely understood.

Objective: The objective of this study was to examine the mechanism underlying the hypoglycemic action of RRK extract in two diabetic animal models: the insulin-deficiency mice, where the insulin deficiency was induced by streptozotocin (STZ), and insulin-resistance mice, where the insulin resistance was induced by a high-fat diet (HFD).

Design: Low (12.5 mg/kg body weight [BW]) and high (50.0 mg/kg BW) doses of RRK extract were orally administered to the mice for 10 successive days (0.25 mL/day/mouse). The protein expression levels of glucose transporter type 4 (GLUT4) in the skeletal muscle and glucose transporter type 2 (GLUT2) in the liver were measured. Blood glucose (BG) levels of STZ-treated mice in insulin tolerance test (ITT) and BG and insulin levels of HFD-fed mice in intraperitoneal glucose tolerance test (IPGTT) were investigated.

Results: In the STZ-treated mice, oral administration of RRK extract lowered BG levels and food intake but increased plasma 1,5-anhydroglucitol level. Moreover, the RRK extract lowered the BG levels of STZ-treated mice as measured by ITT. In the HFD-fed mice, we confirmed that the orally administered RRK extract lowered the BG and the homeostasis model assessment index for insulin resistance. Furthermore, the RRK extract lowered the BG and insulin levels of HFD-fed mice in IPGTT. Regarding the protein levels of GLUT, the orally administered RRK extract increased the GLUT4 level in the skeletal muscle; however, the RRK extract did not alter the GLUT2 level in the liver of either the STZ-treated or the HFD-fed mice.

Discussion: Our study demonstrates that RRK extract can improve impaired glucose tolerance in mouse models of diabetes by enhancing GLUT4 expression in skeletal muscle.

Conclusion: These results suggest that RRK extract could potentially be a functional food for the treatment of diabetes mellitus.

Keywords: GLUT4; diabetes; high fat diet; plasma lipids; red rice koji; streptozotocin.