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Transcellular Barriers to Glucose Delivery in the Body

Authors
  • Klip, Amira
  • De Bock, Katrien
  • Bilan, Philip J.
  • Richter, Erik A.
Type
Published Article
Journal
Annual Review of Physiology
Publisher
Annual Reviews
Publication Date
Feb 12, 2024
Volume
86
Pages
149–173
Identifiers
DOI: 10.1146/annurev-physiol-042022-031657
Source
Annual Reviews
Keywords
License
Green

Abstract

Glucose is the universal fuel of most mammalian cells, and it is largely replenished through dietary intake. Glucose availability to tissues is paramount for the maintenance of homeostatic energetics and, hence, supply should match demand by the consuming organs. In its journey through the body, glucose encounters cellular barriers for transit at the levels of the absorbing intestinal epithelial wall, the renal epithelium mediating glucose reabsorption, and the tight capillary endothelia (especially in the brain). Glucose transiting through these cellular barriers must escape degradation to ensure optimal glucose delivery to the bloodstream or tissues. The liver, which stores glycogen and generates glucose de novo, must similarly be able to release it intact to the circulation. We present the most up-to-date knowledge on glucose handling by the gut, liver, brain endothelium, and kidney, and discuss underlying molecular mechanisms and open questions. Diseases associated with defects in glucose delivery and homeostasis are also briefly addressed. We propose that the universal problem of sparing glucose from catabolism in favor of translocation across the barriers posed by epithelia and endothelia is resolved through common mechanisms involving glucose transfer to the endoplasmic reticulum, from where glucose exits the cells via unconventional cellular mechanisms.

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