D-mannitol modulates glucose uptake ex vivo; suppresses intestinal glucose absorption in normal and type 2 diabetic rats

Mannitol is a widely used reduced-calorie sweetener with limited studies on its anti-hyperglycemic potential. The anti-hyperglycemic potential of mannitol was investigated using different experimental models. Mannitol inhibited α-glucosidase (IC ₅₀ = 180 ± 20% w/v) and α-amylase (IC ₅₀ = 75 ± 20% w/v) activities in a dose dependent (2.5–20% w/v) manner, in vitro, although the effective doses are not gastrointestinally tolerable. Mannitol inhibited glucose absorption (IC ₅₀ = 19 ± 3% w/v) in isolated rat jejunum in a dose dependent (2.5–20% w/v) manner, perhaps by entrapment of glucose molecules. Acute administration of 0.3 g/kg bw reduced small intestinal glucose absorption in type 2 diabetic rats, which was accompanied by reduced blood glucose. The reduced intestinal glucose absorption may be influenced by the concomitant delayed gastric emptying observed in the mannitol-treated diabetic animals. On the other hand, mannitol increased glucose uptake in a yeast cell suspension (GU ₅₀ = 4.7 ± 1.2% w/v), 3T3-L1 adipocytes (GU ₅₀ = 1.2 ± 0.4% w/v) and isolated rat muscle (GU ₅₀ = 25 ± 3% w/v) in a dose dependent manner. In silico docking suggested that GLUT-4 (binding energy = −15.5 kcal/mol) is a possible molecular target of mannitol. Data from this study suggest that mannitol may be used as a dietary supplement in controlling postprandial blood glucose increase by reducing intestinal glucose absorption and increasing muscle glucose uptake, which needs further study.