GLP-1 release and vagal afferent activation mediate the beneficial metabolic and chronotherapeutic effects of D-allulose (Nature communications 2018, 9(1):113)

報告日期: 2019/11/22
報告時間: 16:00/16:50
報告學生: 趙子緯
講評老師: 陳韻雯
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GLP-1 release and vagal afferent activation mediate the beneficial metabolic and chronotherapeutic effects of D-allulose

Iwasaki et al., Nature communications, 2018 Jan 9;9(1):113.

Speaker:Zi-Wei, Zhao(趙子緯)          Time:16:00~16:50, Nov. 22, 2019

Commentator:Dr. Yun-Wen, Chen(陳韻雯老師)        Place:Room 602

Arrhythmic feeding promotes obesity and several metabolic disorders. Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective anti-obesity drugs which can be used to treat not only type 2 diabetes but obesity, hyperphagia, and hypertension. However, GLP-1R agonists may induce CNS-dependent side effects, including eliciting nausea and vomiting, increasing mean heart rate, enhancing sympathetic nervous system tone. D-allulose, a non-calorie sweetener, has been suggested to ameliorate diabetes and obesity, although the mechanism remains unclear. The authors hypothesized that D-allulose stimulates the release of endogenous GLP-1 from intestinal L-cells, which may induce low CNS-dependent side effects, and activates vagal afferent to ameliorate metabolic disorders. The results showed that acute oral administration of D-allulose increased GLP-1 secretion, suppressed food intake and improved glucose tolerance in healthy mice as well as high-fat diet feeding- and genetic mutation (db/db)-induced obesity and diabetic mice. These effects were blocked by GLP-1R blockade, Glp1r knockout mice, and subdiaphragmatic vagotomy. Interestingly, 10-day D-allulose treatment ameliorated light period-specific hyperphagia, visceral obesity, and glucose tolerance. The last results indicated that D-allulose GLP-1R dependently activates vagal afferent neurons and nucleus tractus solitaries which the areas implicated in regulation of feeding. In conclusion, the results suggested that D-allulose is a GLP-1 releaser, which then restricts feeding and balances glucose homeostasis via vagal afferent. Furthermore, as the safety of D-allulose as dietary supplements has been approved by the US Food and Drug Administration, D-allulose represents a more efficacious and safe therapy to ameliorate obesity, diabetes, and metabolic disorders than GLP-1R agonists.

References

  1. Andersen, A., et al. Glucagon-like peptide 1 in health and disease. Nat. Rev. Endocrinol., 14, 390-403 (2018).
  2. Hossain, A., et al. Rare sugar D-allulose: Potential role and therapeutic monitoring in maintaining obesity and type 2 diabetes mellitus. Pharmacol. Ther., 155, 49-59 (2015).