Type 2 diabetes affects arsenic metabolism via transporters in arsenic trioxide treated acute promyelocytic leukemia patients

Environ Toxicol Pharmacol. 2023 Jun:100:104142. doi: 10.1016/j.etap.2023.104142. Epub 2023 May 3.

Abstract

Our study aimed to explore whether type 2 diabetes (T2DM) can affect arsenic metabolism in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide. We found that compared with non-diabetic APL patients, the concentrations of arsenic metabolites in APL patients with T2DM increased significantly and positively correlated with blood glucose (P < 0.05). Meanwhile, APL patients with T2DM were more prone to liver injury and QTc interval prolongation due to altered arsenic methylation capacity. Then we cultured HEK293T cells at different glucose concentrations, and the results showed that the cells with high glucose had higher concentrations of arsenic metabolites compared to other cells. Meanwhile, the high glucose significantly increased the mRNA and protein expression levels of the arsenic uptake transporter AQP7 in HEK293T cells. Overall, our study demonstrated that T2DM can lead to elevated concentrations of arsenic metabolites in APL patients by increasing AQP7 expression.

Keywords: Acute promyelocytic leukemia; Arsenic metabolism; Arsenic trioxide; Transporter; Type 2 diabetes mellitus.

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Arsenic Trioxide / therapeutic use
  • Arsenic* / toxicity
  • Arsenicals* / adverse effects
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucose
  • HEK293 Cells
  • Humans
  • Leukemia, Promyelocytic, Acute* / drug therapy
  • Leukemia, Promyelocytic, Acute* / metabolism
  • Oxides / therapeutic use

Substances

  • Arsenic Trioxide
  • Arsenic
  • Antineoplastic Agents
  • Arsenicals
  • Oxides
  • Glucose