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

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. Popular scientific summary • Red rice koji (RRK) extract lowered blood glucose levels in streptozotocin (STZ)-treated and highfat diet (HFD)-fed mice and food intake in STZ-treated mice. • RRK extract lowered blood glucose levels of STZ-treated mice in insulin tolerance test and blood glucose and insulin levels of HFD-fed mice in intraperitoneal glucose tolerance test. • RRK extract increased glucose transporter type 4 level in the skeletal muscle of both STZ-treated and HFD-fed mice.

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“…The inactivation of GLUT-2 in the liver may lead to impaired glucose-stimulated insulin secretion (41). Impaired expression of GLUT-4 was linked to obesity, type 1 diabetes, and type 2 diabetes (42). In the present study, intervention with SDC increased liver GLUT-2 levels and skeletal muscle GLUT-4 levels in high-fat diet/streptozocininduced T2DM mice, suggesting that SDC may regulate glucose metabolism through the regulation of GLUT-2 and GLUT-4.…”

Impact of Lipids on Insulin Resistance: Insights from Human and Animal Studies

“… Red rice koji extract decreases blood glucose and insulin levels, indicating improved insulin sensitivity. [ 45 ] N/A N/A WT male C57BL/6 J mice, 8 to 10 weeks old dan GRX2-KO mice (n = 64) HFD for 16 weeks Ctrl/WT; HFD/WT; Ctrl/KO; and HFD/KO. (n = 16/group) HFD in mice leads to weight gain, IR, and fat accumulation, affecting brain health, particularly in mice lacking GRX2, a protective protein that suppresses inflammation, oxidative stress, and mitochondrial dysfunction through GSK-3β signaling.…”

Preventive Roles of Rice-koji Extracts and Ergothioneine on Anxiety- and Pain-like Responses under Psychophysical Stress Conditions in Male Mice

“…Lately, consumers have been preferring natural foods, including rice-fermented foods, because of the increased interest in safer diets in Japan [ 2 , 3 ]. Rice- koji , made from Aspergillus oryzae (yellow koji mold), is a readily accessible contributor to nutrition and has been used as a source of rice-fermented food [ 4 , 5 , 6 ]. The beneficial effects of Rice- koji are due to the abundance of substances contained in it that have the potential to regulate bodily function [ 7 ].…”