Metabolic reprogramming in diabetes and other endocrine and metabolic disorders : exploring the Warburg effect, ketones, and SGLT2 inhibitors
(2025) In Reviews in Endocrine and Metabolic Disorders- Abstract
The “Warburg effect”, a metabolic adaptation observed in dividing cells, involves a shift from mitochondrial oxidative phosphorylation to cytoplasmic glucose metabolism. This metabolic process is characterized by increased cellular uptake of glucose and glutamine, elevated intracellular pH and sodium levels, enhanced protection against oxidative stress, altered autophagy, and increased lactate production. Initially identified by Otto Warburg in cancer cells, the Warburg effect is now recognized as a common feature of all dividing cells, prioritizing biomass production for cell proliferation over energy generation for specialized cellular functions. Indeed, the Warburg effect is emerging as an important feature not only in cancer but... (More)
The “Warburg effect”, a metabolic adaptation observed in dividing cells, involves a shift from mitochondrial oxidative phosphorylation to cytoplasmic glucose metabolism. This metabolic process is characterized by increased cellular uptake of glucose and glutamine, elevated intracellular pH and sodium levels, enhanced protection against oxidative stress, altered autophagy, and increased lactate production. Initially identified by Otto Warburg in cancer cells, the Warburg effect is now recognized as a common feature of all dividing cells, prioritizing biomass production for cell proliferation over energy generation for specialized cellular functions. Indeed, the Warburg effect is emerging as an important feature not only in cancer but also in a range of metabolic, endocrine, and neurological chronic disorders, including type 2 diabetes, heart and kidney failure, therapy-refractory epilepsy, Alzheimer's and Parkinson's diseases, chronic fatigue syndrome, and post-viral syndromes. The prevailing notion that “dysfunctional mitochondria” are the primary cause of the “energy deficit” observed in these conditions may be misleading. Instead, this “energy deficit” can result from cells reprogramming their metabolism to support cell division. Additionally, in these disorders, senescent cells are abundant, exhibiting a Warburg-like metabolism with cell cycle arrest and enhanced anabolic activity. This review explores the multifaceted role of the Warburg effect in type 2 diabetes and other metabolic and endocrine chronic disorders and examines the therapeutic potential of different interventions such as intermittent fasting, ketogenic diets, ketone supplements, and sodium/glucose co-transporter 2 inhibitors. Through a comprehensive analysis of existing literature, we aim to shed light on the mechanisms underlying these interventions and their potential impact on disease progression and patient outcomes.
(Less)
- author
- Carrera-Bastos, Pedro LU ; Muskiet, Marcel H.A. ; Mata-Ordoñez, Fernando ; Pruimboom, Leo ; Lucia, Alejandro ; Luque, Raul M. and Muskiet, Frits A.J.
- organization
- publishing date
- 2025
- type
- Contribution to journal
- publication status
- epub
- subject
- keywords
- Diabetes, Heart failure, Ketones, Senescent cells, Sodium/glucose cotransporter, Warburg effect
- in
- Reviews in Endocrine and Metabolic Disorders
- publisher
- Springer
- external identifiers
-
- scopus:105019690989
- pmid:41129010
- ISSN
- 1389-9155
- DOI
- 10.1007/s11154-025-09996-z
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
- id
- 4c89a1ce-20eb-4c3d-9355-ea13dd24e3fa
- date added to LUP
- 2026-01-16 11:58:19
- date last changed
- 2026-01-17 03:00:06
@article{4c89a1ce-20eb-4c3d-9355-ea13dd24e3fa,
abstract = {{<p>The “Warburg effect”, a metabolic adaptation observed in dividing cells, involves a shift from mitochondrial oxidative phosphorylation to cytoplasmic glucose metabolism. This metabolic process is characterized by increased cellular uptake of glucose and glutamine, elevated intracellular pH and sodium levels, enhanced protection against oxidative stress, altered autophagy, and increased lactate production. Initially identified by Otto Warburg in cancer cells, the Warburg effect is now recognized as a common feature of all dividing cells, prioritizing biomass production for cell proliferation over energy generation for specialized cellular functions. Indeed, the Warburg effect is emerging as an important feature not only in cancer but also in a range of metabolic, endocrine, and neurological chronic disorders, including type 2 diabetes, heart and kidney failure, therapy-refractory epilepsy, Alzheimer's and Parkinson's diseases, chronic fatigue syndrome, and post-viral syndromes. The prevailing notion that “dysfunctional mitochondria” are the primary cause of the “energy deficit” observed in these conditions may be misleading. Instead, this “energy deficit” can result from cells reprogramming their metabolism to support cell division. Additionally, in these disorders, senescent cells are abundant, exhibiting a Warburg-like metabolism with cell cycle arrest and enhanced anabolic activity. This review explores the multifaceted role of the Warburg effect in type 2 diabetes and other metabolic and endocrine chronic disorders and examines the therapeutic potential of different interventions such as intermittent fasting, ketogenic diets, ketone supplements, and sodium/glucose co-transporter 2 inhibitors. Through a comprehensive analysis of existing literature, we aim to shed light on the mechanisms underlying these interventions and their potential impact on disease progression and patient outcomes.</p>}},
author = {{Carrera-Bastos, Pedro and Muskiet, Marcel H.A. and Mata-Ordoñez, Fernando and Pruimboom, Leo and Lucia, Alejandro and Luque, Raul M. and Muskiet, Frits A.J.}},
issn = {{1389-9155}},
keywords = {{Diabetes; Heart failure; Ketones; Senescent cells; Sodium/glucose cotransporter; Warburg effect}},
language = {{eng}},
publisher = {{Springer}},
series = {{Reviews in Endocrine and Metabolic Disorders}},
title = {{Metabolic reprogramming in diabetes and other endocrine and metabolic disorders : exploring the Warburg effect, ketones, and SGLT2 inhibitors}},
url = {{http://dx.doi.org/10.1007/s11154-025-09996-z}},
doi = {{10.1007/s11154-025-09996-z}},
year = {{2025}},
}