Erythritol Attenuates Postprandial Blood Glucose by Inhibiting α-Glucosidase

Abstract

Diabetes mellitus (DM) is a serious metabolic disorder, where impaired postprandial blood glucose regulation often leads to severe health complications. The natural chemical erythritol is a C4 polyol approved by the U.S. Food and Drug Administration for use as a sweetener. Here, we examined a potential role for erythritol in the control of postprandial blood glucose levels in DM. An anti-postprandial hyperglycemia effect upon erythritol administration (500 mg kg) was demonstrated in alloxan-induced DM model mice by monitoring changes in blood glucose after intragastric administration of drugs and starch. We also found that erythritol most likely exerts its anti-postprandial hyperglycemic activities by inhibiting α-glucosidase in a competitive manner. This was supported by enzyme activity assays and molecular modeling experiments. In the latter experiments, it was possible to successfully dock erythritol into the catalytic pocket of α-glucosidase, with the resultant interaction likely driven by electrostatic interactions involving Asp215, Asp69, and Arg446 residues. This study suggests that erythritol may not only serve as a glucose substitute but also be a useful agent in the treatment of DM to help manage postprandial blood glucose levels.

An overview on the role of bioactive α-glucosidase inhibitors in ameliorating diabetic complications

“…Erythritol, a sugar alcohol (C4 polyol), occurs naturally in grapes, pears, watermelon, mushrooms and in some fermented items such as sake, wine, etc. ( Shindou et al, 1988 ; Wen et al, 2018 ) [ Fig. 5 ].…”

“…Enzyme kinetics study reveals that erythritol exhibit competitive inhibition by binding to the active site of α-glucosidase. The (-OH) group on C1 atom of erythritol forms hydrogen bonds with Asp69 and Arg446 in active site of α-glucosidase via H113 water molecules and another (-OH) group on C4 atom form identical bonds with Asp215, Arg213, and Asp352 via H132 water molecules, clearly suggesting the occupancy of erythritol in the active site of α-glucosidase ( Wen et al, 2018 ). So, erythritol can be considered as a potential α-glucosidase inhibitor and it can overcome the drawbacks of the traditional α-glucosidase inhibitors due to its negligible side effects and caloric value.…”

Lethal effects of erythritol on the mosquito Aedes aegypti Linnaeus (Diptera: Culicidae)

“…Another possible mode of action is that erythritol could block the digestion of carbohydrates through inhibiting the enzymatic activity of alpha glucosidases. Alpha glucosidase inhibition by erythritol has been demonstrated in a hemipteran (Silva & Terra, ), and modelling studies suggest that erythritol can bind to the catalytic pocket of mouse alpha glucosidase (Wen et al., ). Aedes aegypti alpha glucosidase is expressed in the larval midgut and in the adult salivary glands and has been proposed to play a role in carbohydrate digestion (Ferreira, Romão, Pompílio ‐Melo‐Neto, & Silva‐Filha, ; Marinotti & James, ).…”

“…Another possible mode of action is that erythritol could block the digestion of carbohydrates through inhibiting the enzymatic activity of alpha glucosidases. Alpha glucosidase inhibition by erythritol has been demonstrated in a hemipteran (Silva & Terra, 1995), and modelling studies suggest that erythritol can bind to the catalytic pocket of mouse alpha glucosidase (Wen et al, 2018).…”

Inhibición de la α-glucosidasa mediante flavonoides de origen natural como vía de control en el desarrollo de diabetes mellitus

“…Los oligosacáridos hidrolizados con α-glucosidasa liberan glucosa, lo que finalmente puede conducir enuna hiperglucemia posprandial (3,4). Un aumento en los niveles de glucosa en sangre conduce también a una acelerada glicación, lo que ayuda a la formación de productos finales de glicación avanzada (AGE), aspecto importante ya que se han identificado alteraciones en la estructura y función de las proteínas causadas por la glicación como un vínculo importante entre la diabetes y sus complicaciones graves, como la retinopatía, la neuropatía y las complicaciones cardiovasculares (3,4). Por lo tanto, la inhibición de la hidrólisis de glucosidasa para liberar glucosa es un método adecuado para reducir la hiperglucemia posprandial.…”