title: Xylitol prevents NEFA-induced insulin resistance in rats.
abstract: OBJECTIVE
  Increased NEFA levels, characteristic of type 2 diabetes mellitus, contribute to skeletal muscle insulin resistance. While NEFA-induced insulin resistance was formerly attributed to decreased glycolysis, it is likely that glucose transport is the rate-limiting defect. Recently, the plant-derived sugar alcohol xylitol has been shown to have favourable metabolic effects in various animal models. Furthermore, its derivative xylulose 5-phosphate may prevent NEFA-induced suppression of glycolysis. We therefore examined whether and how xylitol might prevent NEFA-induced insulin resistance.
  
  
  METHODS
  We examined the ability of xylitol to prevent NEFA-induced insulin resistance. Sustained ~1.5-fold elevations in NEFA levels were induced with Intralipid/heparin infusions during 5 h euglycaemic-hyperinsulinaemic clamp studies in 24 conscious non-diabetic Sprague-Dawley rats, with or without infusion of xylitol.
  
  
  RESULTS
  Intralipid infusion reduced peripheral glucose uptake by ~25%, predominantly through suppression of glycogen synthesis. Co-infusion of xylitol prevented the NEFA-induced decreases in both glucose uptake and glycogen synthesis. Although glycolysis was increased by xylitol infusion alone, there was minimal NEFA-induced suppression of glycolysis, which was not affected by co-infusion of xylitol.
  
  
  CONCLUSIONS
  We conclude that xylitol prevented NEFA-induced insulin resistance, with favourable effects on glycogen synthesis accompanying the improved insulin-mediated glucose uptake. This suggests that this pentose sweetener has beneficial insulin-sensitising effects.
authors.affiliation: Diabetes Research Center, Albert Einstein College of Medicine, 1300 Morris Park Ave, Belfer 709, Bronx, NY 10461, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kishore
authors.forename: S
authors.initials: S
authors.lastname: Kehlenbrink
authors.forename: M
authors.initials: M
authors.lastname: Hu
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Gutierrez-Juarez
authors.forename: S
authors.initials: S
authors.lastname: Koppaka
authors.forename: M R
authors.initials: MR
authors.lastname: El-Maghrabi
authors.forename: M
authors.initials: M
authors.lastname: Hawkins
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014993:Xylitol / Q000494:pharmacology*
chemical_list: D005230:Fatty Acids, Nonesterified; D005947:Glucose; D014993:Xylitol