d-allulose Ameliorates Metabolic Dysfunction in C57BL/KsJ-db/db Mice

Molecules. 2020 Aug 11;25(16):3656. doi: 10.3390/molecules25163656.


d-allulose is an uncommon sugar that provides almost no calories when consumed. Its sweetness is 70% that of sucrose. d-allulose is a metabolic regulator of glucose and lipid metabolism. However, few reports concerning its effect on diabetes and related metabolic disturbances in db/db mice are available. In this study, we evaluated d-allulose's effect on hyperglycemia, hyperinsulinemia, diabetes and inflammatory responses in C57BL/KsJ-db/db mice. Mice were divided into normal diet, erythritol supplemented (5% w/w), and d-allulose supplemented (5% w/w) groups. Blood glucose and plasma glucagon levels and homeostatic model assessment (HOMA-IR) were significantly lower in the d-allulose group than in the normal diet group, and plasma insulin level was significantly increased. Further, d-allulose supplement significantly increased hepatic glucokinase activity and decreased hepatic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activity. Expression of glucose transporter 4, insulin receptor substrate 1, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha and AKT serine/threonine kinase 2 were also upregulated by d-allulose supplement in adipocyte and muscle. Finally, d-allulose effectively lowered plasma and hepatic triglyceride and free fatty acid levels, and simultaneously reduced hepatic fatty acid oxidation and carnitine palmitoyl transferase activity. These changes are likely attributable to suppression of hepatic fatty acid synthase and glucose-6-phosphate dehydrogenase activity. Notably, d-allulose also reduced pro-inflammatory adipokine and cytokine levels in plasma. Our results indicate that d-allulose is an effective sugar substitute for improving lipid and glucose metabolism.

Keywords: d-allulose; metabolic syndrome; sugar substitute; type 2 diabetes mellitus.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Fructose / pharmacology*
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / metabolism
  • Hyperglycemia / pathology
  • Hyperinsulinism / drug therapy*
  • Hyperinsulinism / metabolism
  • Hyperinsulinism / pathology
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Insulin / blood
  • Lipids / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains


  • Blood Glucose
  • Insulin
  • Lipids
  • psicose
  • Fructose