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Special Issue "SGLT2 Inhibitors: Emerging "Magic Bullets" Beyond Glycemic Control"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 31 July 2021.

Special Issue Editor

Prof. Dr. Anastasios Lymperopoulos
Guest Editor
Nova Southeastern University, From the Laboratory for the Study of Neurohormonal Control of the Circulation, Fort Lauderdale, United States
Interests: cardiovascular G protein-coupled receptors (GPCRs); heart failure; autonomic control of the circulation; adrenal physiology and pharmacology; adrenergic receptors; angiotensin receptors; signal transduction; gene therapy; aldosterone pharmacology; GPCR-Kinases; arrestins

Special Issue Information

Dear Colleagues,

Originally developed for restoring euglycemia in diabetes mellitus, SGLT2 inhibitors (SGLT2i’s) are increasingly being demonstrated to exert beneficial effects in patients, extending beyond blood glucose regulation. For instance, they reduce cardiovascular disease mortality, ameliorate kidney disease progression, lower blood pressure, and confer weight loss, even in non-diabetics or in people with end-stage chronic kidney disease. Therefore, a lot of information regarding the physiological effects and pharmacological mechanisms of SGLT2i`s remains to be obtained, necessitating more research to fully grasp their therapeutic potential.

On these grounds, this Special Issue of the International Journal of Molecular Sciences is focused on studies that explore the biological and pharmacological effects of SGLT2i`s in human physiology and disease. Investigations with a solid basic/molecular research foundation and/or translational potential are of particular interest, including papers exploring novel molecular and cellular mechanisms underlying the effects of these drugs, as well as pre-clinical investigations testing novel hypotheses that advance the molecular and clinical pharmacology of SGLT2 inhibitors. Original investigations, review articles, and short communications will all be considered. Purely clinical investigations are not suitable but clinical submissions with at least some component of molecular studies are quite welcome.

Suggested disease areas/topics to be covered include (but are by no means limited to) the following:

  • cell biology;
  • signal transduction;
  • autonomic nervous system;
  • atherosclerosis/lipid disorders;
  • cancer;
  • hypertension;
  • cognitive dysfunction/neurodegeneration and other central nervous system (CNS) disorders;
  • heart failure and cardiac arrhythmias;
  • metabolic syndrome/diabetes mellitus;
  • stem cell biology/physiology;
  • inflammatory and/or autoimmune diseases and pain;
  • cardiovascular endocrinology (e.g., adrenal gland and neuronal control of the circulation);
  • end-organ damage and sepsis;
  • respiratory diseases;
  • kidney disorders;
  • vascular pathologies;
  • aging;
  • obesity/adipose tissue biology;
  • drug–drug interactions with other drug classes;
  • adverse effects and toxicology;
  • pharmacogenetics/pharmacogenomics;
  • metabolism and pharmacokinetics in humans;
  • effects in special populations (pediatric, geriatric, pregnancy, etc.);
  • sex differences in drug action/response;
  • cellular energetics/mitochondria;
  • nuclear biology/DNA damage;
  • oxidative stress.

Prof. Dr. Anastasios Lymperopoulos
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


  • diabetes
  • glucose reduction
  • metabolic disorders
  • heart failure
  • cardiovascular disease
  • signal transduction
  • kidney disease
  • hypertension
  • obesity
  • adverse effects
  • neurodegeneration
  • inflammation

Published Papers (1 paper)

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Open AccessArticle
Sodium-Glucose Co-Transporter 2 Inhibitors Correct Metabolic Maladaptation of Proximal Tubular Epithelial Cells in High-Glucose Conditions
Int. J. Mol. Sci. 2020, 21(20), 7676; https://doi.org/10.3390/ijms21207676 - 16 Oct 2020
Glucose filtered in the glomerulus is actively reabsorbed by sodium-glucose co-transporter 2 (SGLT2) in proximal tubular epithelial cells (PTEC) and passively returned to the blood via glucose transporter 2 (GLUT2). Healthy PTEC rely primarily on fatty acid beta-oxidation (FAO) for energy. In phase [...] Read more.
Glucose filtered in the glomerulus is actively reabsorbed by sodium-glucose co-transporter 2 (SGLT2) in proximal tubular epithelial cells (PTEC) and passively returned to the blood via glucose transporter 2 (GLUT2). Healthy PTEC rely primarily on fatty acid beta-oxidation (FAO) for energy. In phase III trials, SGLT2 inhibitors improved outcomes in diabetic kidney disease (DKD). Tubulointerstitial renal fibrosis due to altered metabolic reprogramming of PTEC might be at the root of the pathogenesis of DKD. Here, we investigated the molecular mechanism of SGLT2 inhibitors’ renoprotective effect by examining transcriptional activity of Spp1, which encodes osteopontin, a key mediator of tubulointerstitial renal fibrosis. With primary cultured PTEC from Spp1-enhanced green fluorescent protein knock-in mice, we proved that in high-glucose conditions, increased SGLT2- and GLUT-mediated glucose uptake is causatively involved in aberrant activation of the glycolytic pathway in PTEC, thereby increasing mitochondrial reactive oxygen species (ROS) formation and transcriptional activation of Spp1. FAO activation did not play a direct role in these processes, but elevated expression of a tubular-specific enzyme, myo-inositol oxygenase, was at least partly involved. Notably, canagliflozin blocked overexpression of myo-inositol oxygenase. In conclusion, SGLT2 inhibitors exerted renoprotective effects by inhibiting aberrant glycolytic metabolism and mitochondrial ROS formation in PTEC in high-glucose conditions. Full article
(This article belongs to the Special Issue SGLT2 Inhibitors: Emerging "Magic Bullets" Beyond Glycemic Control)
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