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Simultaneous SGLT2 inhibition and caloric restriction improves insulin resistance and kidney function in OLETF rats

Manuel A Cornejo1, Eira Jardines1, Akira Nishiyama2

  • 1Department of Molecular & Cell Biology, School of Natural Sciences, University of California, Merced, CA, USA.

Molecular and Cellular Endocrinology
|November 18, 2022
PubMed

Insights

Combining SGLT2 inhibitors (SGLT2i) with caloric restriction (CR) significantly improves metabolic syndrome markers in rats. This combination therapy enhances insulin sensitivity and kidney function more effectively than either intervention alone.

Area of Science:

  • Metabolic Syndrome Research
  • Pharmacology and Therapeutics
  • Renal and Cardiovascular Health

Background:

  • Sodium-glucose cotransporter 2 inhibitors (SGLT2i) show promise for type 2 diabetes management.
  • Caloric restriction (CR) is a known strategy for improving obesity and insulin resistance.
  • Simultaneous application of SGLT2i and CR may offer synergistic benefits for metabolic health.

Purpose of the Study:

  • To investigate the combined effects of SGLT2 inhibitors and caloric restriction on metabolic syndrome.
  • To evaluate the impact on carbohydrate metabolism, body mass, insulin resistance, blood pressure, and kidney function.

Main Methods:

  • Male Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were used.
  • Treatments included SGLT2 inhibitor (luseogliflozin) and/or 30% CR for specified durations.
  • Measurements included body mass, systolic blood pressure (SBP), insulin resistance index (IRI), and kidney function markers (creatinine clearance, albuminuria).

Main Results:

  • CR maintained body mass; SGLT2i alone did not affect body mass.
  • Combined SGLT2i and CR decreased SBP and IRI more than SGLT2i alone in OLETF rats.
  • CR reduced albuminuria independently of SGLT2i.
  • Simultaneous treatment improved creatinine clearance compared to ad libitum feeding.

Conclusions:

  • SGLT2 inhibitors alone showed limited benefits for insulin resistance, kidney function, or blood pressure.
  • Combined SGLT2i and CR demonstrated more profound improvements than CR alone.
  • The combination therapy enhanced metabolic parameters without causing chronic hypoglycemia.
Keywords:
AMPKAlbuminGLUT4HexokinaseInsulin receptorSBP

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