Reinterpreting Cardiorenal Protection of Renal Sodium-Glucose Cotransporter 2 Inhibitors via Cellular Life History Programming.

Abstract:

:Cardiovascular outcome trials have provided evidence that sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment is associated with remarkably favorable cardiovascular outcomes. Here, we offer a novel hypothesis that may encompass many of these hypothetical mechanisms, i.e., the ability of SGLT2i to modify the trajectory of cell response to a toxic environment through modifications of cellular life history programs, either the defense program or the dormancy program. The choice between these programs is mainly determined by the environment. Hyperglycemia can be considered a toxic determinant able to interfere with the basic programs of cell evolution. While the defense program is characterized by activation of the immune response and anabolic metabolism, the dormancy program is an energy-preserving state with high resistance to environmental stressors, and it has strong analogy with animal hibernation where fuel is stored, metabolic rate is suppressed, and insulin secretion is reduced. The metabolic changes that follow treatment with SGLT2i are reminiscent of the metabolic picture characteristic of the dormancy program. Therefore, we hypothesize that the beneficial cardioprotective effects of SGLT2i may be related to their ability to switch cell life programming from a defense to a dormancy state, thus lending additional benefit.

journal_name

Diabetes Care

journal_title

Diabetes care

authors

Avogaro A,Fadini GP,Del Prato S

doi

10.2337/dc19-1410

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

501-507

issue

3

eissn

0149-5992

issn

1935-5548

pii

dc19-1410

journal_volume

43

pub_type

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