PuSH - Publication Server of Helmholtz Zentrum München: Metabolic effects of SGLT2i and metformin on 3-hydroxybutyric acid and lactate in db/db mice.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Harada, M. ; Han, S. ; Shi, M. ; Ge, J. ; Yu, S. ; Adam, J. ; Adamski, J. ; Scheerer, M.F. ; Neschen, S. ; Hrabě de Angelis, M. ; Wang-Sattler, R.

Metabolic effects of SGLT2i and metformin on 3-hydroxybutyric acid and lactate in db/db mice.

Int. J. Biol. Macromol. 265:130962 (2024)

Publ. Version/Full Text

DOI

PMC

	Open Access Hybrid

Abstract
Metrics
Extra information

Combining a Sodium-Glucose-Cotransporter-2-inhibitor (SGLT2i) with metformin is recommended for managing hyperglycemia in patients with type 2 diabetes (T2D) who have cardio-renal complications. Our study aimed to investigate the metabolic effects of SGLT2i and metformin, both individually and synergistically. We treated leptin receptor-deficient (db/db) mice with these drugs for two weeks and conducted metabolite profiling, identifying 861 metabolites across kidney, liver, muscle, fat, and plasma. Using linear regression and mixed-effects models, we identified two SGLT2i-specific metabolites, X-12465 and 3-hydroxybutyric acid (3HBA), a ketone body, across all examined tissues. The levels of 3HBA were significantly higher under SGLT2i monotherapy compared to controls and were attenuated when combined with metformin. We observed similar modulatory effects on metabolites involved in protein catabolism (e.g., branched-chain amino acids) and gluconeogenesis. Moreover, combination therapy significantly raised pipecolate levels, which may enhance mTOR1 activity, while modulating GSK3, a common target of SGLT2i and 3HBA inhibition. The combination therapy also led to significant reductions in body weight and lactate levels, contrasted with monotherapies. Our findings advocate for the combined approach to better manage muscle loss, and the risks of DKA and lactic acidosis, presenting a more effective strategy for T2D treatment.

Impact Factor

Scopus SNIP

Altmetric

7.700

0.000