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Modulatory effect of empagliflozin on cellular parameters of endocrine pancreas in experimental pre-diabetes

Ahmed A M Abdel-Hamid1, Alaa El-Din L Firgany2

  • 1Department of Histology and Cell Biology, Faculty of Medicine, Mansoura University, Egypt.

Annals of Anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft
|May 21, 2019
PubMed

Insights

Empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), normalized enlarged pancreatic islets in pre-diabetes (Pre-DM). EMPA treatment corrected beta-cell mass and improved glucose homeostasis, suggesting a local anti-inflammatory effect.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Pharmacology

Background:

  • Pre-diabetes (Pre-DM) is characterized by pancreatic islet structural changes.
  • The therapeutic effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i), such as empagliflozin (EMPA), on pancreatic islet structure in Pre-DM are not well understood.

Purpose of the Study:

  • To investigate the impact of EMPA on the structural and cellular composition of pancreatic islets in a Pre-DM model.
  • To evaluate the effects of EMPA on islet cell mass, neogenesis, apoptosis, and inflammatory markers in Pre-DM.

Main Methods:

  • Administration of EMPA to a Pre-DM animal model.
  • Histological analysis of pancreatic islets to assess size, islet mass, and cell composition (beta-cells and alpha-cells).
  • Measurement of apoptotic markers (caspase-3, Bcl-2) and inflammatory cytokines.

Main Results:

  • EMPA treatment restored enlarged islets of Langerhans to normal size in Pre-DM animals.
  • EMPA corrected the imbalanced ratio of beta-cells and alpha-cells, reduced increased islet and beta-cell mass, and decreased neogenesis.
  • EMPA administration normalized caspase-3 and Bcl-2 levels, and significantly reduced elevated inflammatory cytokines.

Conclusions:

  • Empagliflozin effectively reverses structural and cellular abnormalities in pancreatic islets of Pre-DM.
  • EMPA improves glucose homeostasis in Pre-DM, likely through local pleotropic effects on islet cells and reduction of inflammation.
Keywords:
EmpagliflozinInsulin resistanceIslets neogenesisPrediabetesSGLT2iβ-cells

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