Journal
DIABETOLOGIA
Volume 55, Issue 6, Pages 1808-1812Publisher
SPRINGER
DOI: 10.1007/s00125-012-2527-z
Keywords
Insulin resistance; NEFA; Type 2 diabetes mellitus; Xylitol
Categories
Funding
- National Institutes of Health [DK48321, DK 45024, DK69861, K23 RR023335, P01-AG021654]
- American Diabetes Association
- Albert Einstein Diabetes Research and Training Center [DK 20541]
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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. We examined the ability of xylitol to prevent NEFA-induced insulin resistance. Sustained similar to 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. Intralipid infusion reduced peripheral glucose uptake by similar to 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. 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.
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