The Ang III/AT2R Pathway Enhances Glucose Uptake by Improving GLUT1 Expression in 3T3-L1 Adipocytes

Biol Pharm Bull. 2021;44(7):1014-1018. doi: 10.1248/bpb.b20-00946.

Abstract

Angiotensin III (Ang III) is a heptapeptide derived from Ang II that has been confirmed as the preferred agonist of angiotensin II type 2 receptor (AT2R). Recent studies have revealed AT2R mainly exerts anti-inflammation effects. However, the effects of the Ang III/AT2R pathway on adipocytes remain unknown. Here, the effects of Ang III on glucose uptake were examined. The results showed that AT2R expression was upregulated during adipogenesis in 3T3-L1 preadipocytes, whereas AT1R expression was diminished. Also, Ang III (10 nM) significantly increased glucose uptake by 3T3-L1 adipocytes, which was blocked by PD123319, an AT2R blocker, but not by irbesartan, an AT1R blocker. Ang III also induced the expression of glucose transporter type 1 (GLUT1). These stimulatory effects were inhibited by pretreatment with PD123319, but not with irbesartan. Together, these results indicate that Ang III enhances glucose uptake by upregulating GLUT1 expression via AT2R.

Keywords: adipocyte; angiotensin II type 2 receptor; angiotensin III; glucose transporter type 1.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism*
  • Angiotensin III / metabolism*
  • Animals
  • Deoxyglucose / pharmacology
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism*
  • Mice
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptor, Angiotensin, Type 2 / genetics
  • Receptor, Angiotensin, Type 2 / metabolism*
  • Signal Transduction

Substances

  • Glucose Transporter Type 1
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Slc2a1 protein, mouse
  • Angiotensin III
  • Deoxyglucose
  • Glucose