Anekomochi glutinous rice provides low postprandial glycemic response by enhanced insulin action via GLP-1 release and vagal afferents activation

Abstract

Glutinous rice (mochi rice), compared to non-glutinous rice (uruchi rice), exhibits a wide range of glycemic index (GI) values, from low to high. However, the underlying mechanisms behind the variation in GI values remain poorly understood. In this study, we aimed to identify rice cultivars with a low postprandial glycemic response and investigate the mechanisms, focusing on insulin and incretin hormones. We examined seven glutinous rice cultivars and three non-glutinous rice cultivars. We discovered that Anekomochi, a glutinous rice cultivar, has the lowest postprandial glycemic response. Anekomochi significantly enhanced glucagon-like peptide-1 (GLP-1) secretion while suppressing insulin secretion. These effects were completely blunted by inhibiting GLP-1 receptor signaling and denervating the common hepatic branch of vagal afferent nerves that are crucial for sensing intestinal GLP-1. Our findings demonstrate that Anekomochi markedly enhances insulin action via GLP-1 release and vagal afferent neural pathways, thereby leading to a lower postprandial glycemic response.

Keywords: GLP-1; Glutinous rice; Insulin; Postprandial glycemic response; Vagal afferent nerves.

Fig. 1

Changes in blood glucose levels after administration of aqueous solutions of glucose, non-glutinous rice (Hinohikari), and glutinous rice (Anekomochi) in mice. Blood glucose levels (A) and their area under the curve for the increase in blood glucose (AUC for ΔBG) during 0–120 min (B) after peroral (po) administration of glucose (2 g/kg, filled circles, n = 48), Hinohikari (2.59 g/kg, gray circles, n = 23), or Anekomochi (2.71 g/kg, open circles, n = 12) into the stomach of overnight-fasted C57BL/6 J mice using a stainless steel feeding needle. The starch content was standardized to 2 g/kg in all groups. The numbers inside the bars (B) indicate the sample size. Glucose group was included in all experiments conducted on different days as a positive control. The present data were selected from the results in Supplementary Fig. 1. Different alphabet letters within the same time point indicate p < 0.05 by two-way ANOVA followed by Tukey’s test in A, and **p < 0.01 by one-way ANOVA followed by Tukey’s test in B

Fig. 2

Comparison of blood glucose increase after administration of three non-glutinous rice cultivars, seven glutinous rice cultivars, and glucose in mice. Normalized change in blood glucose (ΔBG) levels at 15 min (A) and 30 min (B), and the AUC for the increase in blood glucose (AUC for ΔBG) during 0–30 min (C) and 0–120 min (D) after po administration of glucose (2 g/kg, filled bars, n = 48), three non-glutinous rice cultivars (2.59–2.66 g/kg, gray bars, n = 11–23), or seven glutinous rice cultivars (2.50–2.90 g/kg, open bars, n = 12) in C57BL/6J mice fasted overnight. The starch content was standardized to 2 g/kg in all groups. Glucose group was included in all experiments conducted on different days, and the ΔBG and AUCs of all rice-administered groups were normalized based on the results of the glucose group from experiments conducted on the same day. These data were obtained from the data in Supplementary Fig. 1. The numbers inside the bars indicate the sample size. **p < 0.01, *p < 0.05 by one-way ANOVA followed by Dunnett’s test (vs. Hinohikari group), and ##p < 0.01, #p < 0.05 by one-way ANOVA followed by Dunnett’s test (vs. glucose group)

Fig. 3

Anekomochi potentiates the increase in plasma GLP-1 levels more than Hinohikari. Fifteen min after po administration of the rice solution, blood was collected from the tail vein (A, conscious) or portal vein (B–E, anesthetized) in independent experiments. Hinohikari (2.59 g/kg), Shimizumochi (2.61 g/kg), Habutaemochi (2.78 g/kg), Anekomochi (2.71 g/kg), or Hong Xie Nuo (2.65 g/kg) were administered to C57BL/6 J mice fasted overnight. The starch content was standardized to 2 g/kg in all groups. Blood glucose (A, B), plasma insulin (C), total GLP-1 (D), and total GIP (E) concentrations were measured. n = 12–23 in A and n = 7–8 in B–E. **p < 0.01, *p < 0.05 by one-way ANOVA followed by Tukey’s test

Fig. 4

The low postprandial glycemic response of Anekomochi is due to GLP-1 receptor signaling. Saline (5 ml/kg, A–D) or GLP-1 receptor antagonist exendin(9-39) amide (Ex(9–39), 600 nmol/5 ml/kg, E–H) was ip injected 15 min prior to po administration of Hinohikari (2.59 g/kg) or Anekomochi (2.71 g/kg) in C57BL/6 J mice fasted overnight. Blood glucose (A, E) and plasma insulin (C, G) were measured, and AUCs for the increase in blood glucose (AUC for ΔBG) during 0–120 min (B, F) and HOMA-IR, an indicator of insulin action (D, H) were calculated. n = 9. Changes in blood glucose (I) and their AUC (J) after administration of Hinohikari or Anekomochi in Glp1r KO mice were measured. n = 11. **p < 0.01, *p < 0.05 by two-way ANOVA followed by Bonferroni’s test in A, C, D. **p < 0.01 by unpaired t-test in B

Fig. 5

The vagal afferents of the common hepatic branch are essential for the low postprandial glycemic response of Anekomochi. Hinohikari (2.59 g/kg) or Anekomochi (2.71 g/kg) was po administered to sham-operated mice (A, B, n = 6; E, F, n = 5), surgically hepatic vagotomized mice (C, D, n = 6), or mice with chemical deafferentation of the common hepatic vagus nerve (G, H, n = 6), which were fasted overnight. Blood glucose was measured, and the AUCs for the increase in blood glucose (AUC for ΔBG) during 0–120 min were calculated. **p < 0.01, *p < 0.05 by two-way ANOVA followed by Bonferroni’s test in A, E. **p < 0.01, *p < 0.05 by unpaired t-test in B, F