Xylitol prevents NEFA-induced insulin resistance in rats

P. Kishore, S. Kehlenbrink, M. Hu, K. Zhang, R. Gutierrez-Juarez, S. Koppaka, M. R. El-Maghrabi, M. Hawkins

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Aims/hypothesis 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 NEFAinduced 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 NEFAinduced 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/interpretation 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.

Original languageEnglish (US)
Pages (from-to)1808-1812
Number of pages5
JournalDiabetologia
Volume55
Issue number6
DOIs
StatePublished - Jun 1 2012

Keywords

  • Insulin resistance
  • NEFA
  • Type 2 diabetes mellitus
  • Xylitol

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Kishore, P., Kehlenbrink, S., Hu, M., Zhang, K., Gutierrez-Juarez, R., Koppaka, S., El-Maghrabi, M. R., & Hawkins, M. (2012). Xylitol prevents NEFA-induced insulin resistance in rats. Diabetologia, 55(6), 1808-1812. https://doi.org/10.1007/s00125-012-2527-z