Studies on the possible mechanisms behind the anti-diabetic effects of Xylitol.
Background and Objectives: Sugar substitutes have gained popularity in the management of diabetes, obesity and related diseases, due to their low calorie content compared to sucrose. Recent studies have reported that xylitol, a commonly used sugar alcohol has anti-diabetic properties. This study was therefore conducted to investigate the possible mechanism(s) behind the anti-diabetic effects of xylitol. Materials and Methods: This study was carried out by investigating both in vitro, ex vivo and in vivo mechanisms. For in vitro studies, the inhibitory effects of different concentrations of xylitol (2.5, 5, 10, 20, 30 and 40%) on carbohydrate hydrolyzing and digestive enzymes; alpha-amylse and alpha-glucosidase were investigated. For the ex vivo studies, seven-week-old normal adult male Sprague-Dawley rats (B.W. 180-200 g) were sacrificed and the jejunum and psoas muscles were collected. The effect of increasing concentrations of xylitol (10, 20 and 40%) on intestinal glucose absorption was then examined in isolated rat jejunum. A 3 mM acarbose was used as positive control. Additionally, the effect of increasing concentrations of xylitol on muscle glucose uptake, with and without insulin (100 mU/mL) was investigated in the isolated rat psoas muscles, when 1mg/mL metformin was used as positive control. For the in vivo studies, adult Spagrue Dawley rats were randomly divided into five groups: normal control (NC), normal xylitol (NXYL), diabetic control (DBC), diabetic xylitol (DXYL) and diabetic acarbose (DBA). Type 2 diabetes was induced in the DBC, DXYL and DBA groups. After confirmation of diabetes, animals were fasted overnight for 16 hours, and a single bolus dose of either glucose (for NC and DBC groups) or glucose and xylitol (for NXYL and DXYL groups) or glucose and acarbose (for DBA group) solutions was orally administered to rats along side with 0.05% w/v phenol red as recovery marker. Animals were sacrificed exactly 1 hr after dose administration, and glucose absorption and related parameters were estimated in different segments of the gastrointestinal tract (GIT). Results: Increasing concentrations of xylitol showed increasing inhibition of 4 U/mL alpha-amylase (IC₅₀ = 21.69 xylitol) and 1 U/mL alpha-glucosidase (IC₅₀ = 17.58 xylitol) activities with the highest inhibition at 30% and 40%. Also increasing concentrations of xylitol showed lower glucose intestinal absorption, which was significantly lower at 40% Xylitol compared to the control, 10 and 20% xylitol, but only relatively lower compared to 3mM acarbose. Furthermore, increasing concentrations of xylitol showed increasing glucose muscle uptake, which was significantly higher at 40% Xylitol compared to the control, but only relatively higher compared to 10, 20% xylitol and 1 mg/mL metformin. The presence of insulin did not significantly affect muscle glucose uptake of xylitol. Additionally, oral single bolus dose of xylitol inhibited small intestinal glucose absorption, delayed gastric emptying and accelerated digesta transit in the GIT compared to the respective controls. Acarbose did not significantly affect intestinal glucose absorption in both in vivo and in vitro conditions. Discussion and conclusion: The anti-diabetic effects of xylitol may not only be due to the slower gastric emptying and lower carbohydrate digestion and glucose absorption from the small intestinal mucosa. It may also be due to improving insulin action or exhibiting an insulin-like effect on skeletal muscle, thus increasing muscle glucose uptake and utilization, which may also be mimicked under in vivo conditions.