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Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes
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Sodium-glucose cotransporter-2 inhibitors protect tissues via cellular and mitochondrial pathways: Experimental and

Raúl Lelio Sanz1, Sebastián García Menéndez1,2, Felipe Inserra3

  • 1Department of Pathology, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina.

World Journal of Experimental Medicine
|July 1, 2024
PubMed

Insights

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) show promise in treating cardiovascular disease (CVD) linked to metabolic disorders. These drugs improve mitochondrial function, reduce oxidative stress, and enhance cellular repair, offering potential benefits for heart health.

Area of Science:

  • Cardiovascular Science
  • Metabolic Disorders
  • Mitochondrial Biology

Background:

  • Mitochondrial dysfunction drives cardiovascular disease (CVD) in metabolic syndrome and diabetes, increasing reactive oxygen species (ROS), oxidative stress, and inflammation.
  • Reduced sirtuin (SIRT) activity exacerbates oxidative stress, while impaired mitochondrial energy production is common in metabolic disorders.
  • Angiotensin II contributes to CVD by promoting ROS production.

Purpose of the Study:

  • To explore the therapeutic potential of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in mitigating mitochondrial dysfunction and oxidative stress associated with CVD.
  • To investigate the impact of SGLT2i on cellular metabolism, autophagy, and mitophagy in the context of metabolic disorders and CVD.

Main Methods:

  • Review of randomized clinical trials and existing literature on SGLT2i effects in patients with type 2 diabetes and CVD.
  • Analysis of the molecular mechanisms underlying SGLT2i action, including effects on mitochondrial efficiency, ROS production, and inflammatory pathways.
  • Examination of the role of sirtuins (SIRTs) and 5' adenosine monophosphate-activated protein kinase (AMPK) signaling in mediating SGLT2i benefits.

Main Results:

  • SGLT2i treatment improves cardiac function and reduces cardiovascular and renal events in clinical trials.
  • SGLT2i enhance mitochondrial efficiency, decrease oxidative stress and inflammation, and strengthen cardiovascular tissues.
  • High SIRT levels and AMPK signaling, stimulated by SGLT2i, promote ketosis, which upregulates autophagy and mitophagy for cellular protection.

Conclusions:

  • SGLT2i demonstrate significant potential for treating cardiovascular disease in patients with metabolic disorders.
  • SGLT2i positively influence key pathways involved in cellular metabolism, oxidative stress, and tissue repair, offering cardioprotective effects.
  • While proposed as anti-aging agents, further rigorous research is required to validate the anti-aging potential of SGLT2i.
Keywords:
Cardiovascular diseasesInflammationMitochondrial dysfunctionOxidative stressSirtuinsSodium-glucose cotransporter-2 inhibitors

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