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SGLT1: A Potential Drug Target for Cardiovascular Disease

Mengnan Zhao1, Na Li1, Hong Zhou1

  • 1Department of Endocrinology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

Drug Design, Development and Therapy
|July 12, 2023
PubMed

Insights

Sodium-glucose cotransporter-2 (SGLT2) inhibitors may protect the heart by inhibiting SGLT1, which is highly expressed in the myocardium. This review explores SGLT1

Area of Science:

  • Cardiovascular Research
  • Metabolic Diseases
  • Pharmacology

Background:

  • Sodium-glucose cotransporter 1 (SGLT1) and SGLT2 are key in glucose reabsorption.
  • SGLT2 inhibitors offer cardiovascular protection beyond glucose lowering.
  • SGLT1, not SGLT2, is highly expressed in the heart, suggesting a role in cardiovascular effects.

Purpose of the Study:

  • To review the cardioprotective effects of SGLT1 inhibition.
  • To elucidate the molecular mechanisms underlying SGLT1 inhibition's cardiac benefits.
  • To explore the potential of selective SGLT1 inhibitors for cardiac therapy.

Main Methods:

  • Review of preclinical studies on SGLT1 inhibition in cardiac cells (cardiomyocytes, endothelial cells, fibroblasts).
  • Analysis of molecular pathways involved in SGLT1-mediated cardioprotection.
  • Synthesis of existing clinical trial data on SGLT2 inhibitors and cardiovascular outcomes.

Main Results:

  • SGLT1 inhibition demonstrates protective effects against cardiac oxidative stress, inflammation, fibrosis, apoptosis, and mitochondrial dysfunction.
  • Evidence suggests SGLT1 inhibition contributes to the cardiovascular benefits of SGLT2 inhibitors.
  • Preclinical data support SGLT1's role in various cardiac pathologies.

Conclusions:

  • SGLT1 inhibition presents a promising therapeutic strategy for cardiovascular diseases.
  • Selective SGLT1 inhibitors may offer a novel approach to cardiac-specific treatment.
  • Further research into SGLT1-targeted therapies is warranted.
Keywords:
SGLT1 inhibitorcardioprotectionheart failuremolecular mechanismsodium glucose cotransporter 1

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