The metabolism and transport of 1,5-anhydroglucitol in cells

Acta Diabetol. 2018 Mar;55(3):279-286. doi: 10.1007/s00592-017-1093-8. Epub 2018 Jan 9.

Abstract

Aims: Our previous studies demonstrated that serum 1,5-anhydroglucitol (1,5-AG) levels increased slightly rather than declined after an acute glucose load. Therefore, the current study aims at exploring the transport and metabolic characteristics of 1,5-AG, as well as the effect of glucose on 1,5-AG transport.

Methods: Km and Vmax were determined to measure the affinity of glucose oxidase (GOD) and hexokinase (HK) for 1,5-AG and glucose. HepG2, C2C12, and primary mouse hepatocytes were incubated for 2 h with 1,5-AG at concentrations of 0, 80, and 160 μg/mL. Then, intracellular and extracellular concentrations of 1,5-AG were measured before and after washing with PBS to evaluate the transport and metabolic rates of 1,5-AG. In addition, the influence of an acute glucose load on the transport of 1,5-AG was studied.

Results: The affinity of GOD and HK for 1,5-AG is 5 and 42.5% of that for glucose, respectively. Moreover, there is no de novo synthesis of 1,5-AG, and its metabolic rate is < 3%. After a 2 h incubation with additional 1,5-AG, the intracellular levels of 1,5-AG were 50-80% of extracellular levels. Moreover, intracellular 1,5-AG concentrations decreased rapidly and reached zero following the removal of 1,5-AG from the external medium. In addition, an acute glucose load can affect the dynamic balance of 1,5-AG, causing the intracellular 1,5-AG levels to decline significantly and the extracellular levels to increase slightly in HepG2 cells.

Conclusions: Unlike glucose, 1,5-AG is hard to be metabolized in vivo, and its transport is influenced by an acute glucose load in hepatocytes.

Keywords: 1,5-anhydroglucitol; Glucose load; Glucose oxidase; Hexokinase; Metabolism; Transport.

MeSH terms

  • Animals
  • Biological Transport
  • Cells, Cultured
  • Deoxyglucose / metabolism*
  • Deoxyglucose / pharmacokinetics
  • Glucose / metabolism
  • Glucose Oxidase / metabolism
  • Hep G2 Cells
  • Hepatocytes / metabolism*
  • Hexokinase / metabolism
  • Humans
  • Intracellular Fluid / chemistry
  • Intracellular Fluid / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL

Substances

  • 1,5-anhydroglucitol
  • Deoxyglucose
  • Glucose Oxidase
  • Hexokinase
  • Glucose