title: The effects of critical illness on intestinal glucose sensing, transporters, and absorption.
abstract: OBJECTIVE
  Providing effective enteral nutrition is important during critical illness. In health, glucose is absorbed from the small intestine via sodium-dependent glucose transporter-1 and glucose transporter-2, which may both be regulated by intestinal sweet taste receptors. We evaluated the effect of critical illness on glucose absorption and expression of intestinal sodium-dependent glucose transporter-1, glucose transporter-2, and sweet taste receptors in humans and mice.
  
  
  METHODS
  Prospective observational study in humans and mice.
  
  
  METHODS
  ICU and university-affiliated research laboratory.
  
  
  METHODS
  Human subjects were 12 critically ill patients and 12 healthy controls. In the laboratory 16-week-old mice were studied.
  
  
  METHODS
  Human subjects underwent endoscopy. Glucose (30 g) and 3-O-methylglucose (3 g), used to estimate glucose absorption, were infused intraduodenally over 30 minutes. Duodenal mucosa was biopsied before and after infusion. Mice were randomized to cecal ligation and puncture to model critical illness (n = 16) or sham laparotomy (control) (n = 8). At day 5, mice received glucose (100 mg) and 3-O-methylglucose (10 mg) infused intraduodenally prior to mucosal tissue collection.
  
  
  RESULTS
  Quantitative polymerase chain reaction was performed to measure absolute (human) and relative levels of sodium-dependent glucose transporter-1, glucose transporter-2, and taste receptor type 1 member 2 (T1R2) transcripts. Blood samples were assayed for 3-O-methylglucose to estimate glucose absorption. Glucose absorption was three-fold lower in critically ill humans than in controls (p = 0.002) and reduced by a similar proportion in cecal ligation and puncture mice (p = 0.004). In critically ill patients, duodenal levels of sodium-dependent glucose transporter-1, glucose transporter-2, and T1R2 transcript were reduced 49% (p < 0.001), 50% (p = 0.009), and 85% (p = 0.007), whereas in the jejunum of cecal ligation and puncture mice sodium-dependent glucose transporter-1, glucose transporter-2, and T1R2 transcripts were reduced by 55% (p < 0.001), 50% (p = 0.002), and 69% (p = 0.004).
  
  
  CONCLUSIONS
  Critical illness is characterized by markedly diminished glucose absorption, associated with reduced intestinal expression of glucose transporters (sodium-dependent glucose transporter-1 and glucose transporter-2) and sweet taste receptor transcripts. These changes are paralleled in cecal ligation and puncture mice.
authors: 1Discipline of Acute Care Medicine, University of Adelaide, North Terrace, Adelaide, South Australia, Australia. 2Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 3Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 4Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 5Discipline of Medicine, Nerve-Gut Research Laboratory, Level-1 Hanson Institute, Adelaide, South Australia, Australia.
authors: Adam M
authors: AM
authors: Deane
authors: Chris K
authors: CK
authors: Rayner
authors: Alex
authors: A
authors: Keeshan
authors: Nada
authors: N
authors: Cvijanovic
authors: Zelia
authors: Z
authors: Marino
authors: Nam Q
authors: NQ
authors: Nguyen
authors: Bridgette
authors: B
authors: Chia
authors: Matthew J
authors: MJ
authors: Summers
authors: Jennifer A
authors: JA
authors: Sim
authors: Theresia
authors: T
authors: van Beek
authors: Marianne J
authors: MJ
authors: Chapman
authors: Michael
authors: M
authors: Horowitz
authors: Richard L
authors: RL
authors: Young
mesh_terms: D019325:3-O-Methylglucose / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D016638:Critical Illness; D004195:Disease Models, Animal; D004386:Duodenum / Q000503:physiopathology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism / Q000502:physiology; D051273:Glucose Transporter Type 2 / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007422:Intestines / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism / Q000502:physiology; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism / Q000502:physiology; D055815:Young Adult
chemical_list: D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D043562:Receptors, G-Protein-Coupled; D051269:Sodium-Glucose Transporter 1; C431926:taste receptors, type 1; D019325:3-O-Methylglucose; D005947:Glucose