Dataset Information

Metabolic reconfiguration through SGLT2 inhibition improves metabolic waste excretion

ABSTRACT: Dapagliflozin is a member of a new class of medication called gliflozins indicated for the treatment of diabetes and has recently been also approved for the treatment of kidney and heart diseases. Gliflozins lower blood glucose levels by inhibition of the sodium glucose co-transporter 2 (SGLT2), which is predominantly expressed in the S1 segment of renal proximal tubules and responsible for >90% of renal glucose reabsorption. Renal and cardio protection by gliflozins cannot be solely explained by blood glucose lowering. To gain further mechanistic insights, we determined the metabolomic and proteomic signature of dapagliflozin in a murine model of diabetes. Male C57BL/6 non-diabetic wildtype and littermate Ins2 (Akita) diabetic mice, both fed a Western diet for 5 weeks, were given dapagliflozin (10 mg/kg diet) or vehicle for one week (4 groups, N=8/group). Blood and urine glucose levels confirmed the expected treatment response. We analyzed metabolome, proteome and phosphoproteome for a range of tissues (kidney, liver, heart, smooth muscle, white adipose tissue) and body fluids (serum, urine, erythrocytes), and extended the analysis to the gut metaproteome.

INSTRUMENT(S):

ORGANISM(S): Mouse Gut Metagenome Mus Musculus (mouse)

TISSUE(S): Heart, Skeletal Muscle, Liver, White Adipose Tissue, Feces, Kidney

SUBMITTER: Anja Billing

LAB HEAD: Markus Rinschen

PROVIDER: PXD036817 | Pride | 2026-02-09

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	210830_AB_SGLT2i_Heart_Akita_F.msf	Msf
	210830_AB_SGLT2i_Heart_Akita_F.mzML	Mzml
	210830_AB_SGLT2i_Heart_Akita_F.mzid.gz	Mzid
	210830_AB_SGLT2i_Heart_Akita_F1.raw	Raw
	210830_AB_SGLT2i_Heart_Akita_F2.raw	Raw

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Publications

Metabolic Communication by SGLT2 Inhibition.

Billing Anja M AM Kim Young Chul YC Gullaksen Søren S Schrage Benedikt B Raabe Janice J Hutzfeldt Arvid A Demir Fatih F Kovalenko Elina E Lassé Moritz M Dugourd Aurelien A Fallegger Robin R Klampe Birgit B Jaegers Johannes J Li Qing Q Kravtsova Olha O Crespo-Masip Maria M Palermo Amelia A Fenton Robert A RA Hoxha Elion E Blankenberg Stefan S Kirchhof Paulus P Huber Tobias B TB Laugesen Esben E Zeller Tanja T Chrysopoulou Maria M Saez-Rodriguez Julio J Magnussen Christina C Eschenhagen Thomas T Staruschenko Alexander A Siuzdak Gary G Poulsen Per L PL Schwab Clarissa C Cuello Friederike F Vallon Volker V Rinschen Markus M MM

Circulation 20231228 11

<h4>Background</h4>SGLT2 (sodium-glucose cotransporter 2) inhibitors (SGLT2i) can protect the kidneys and heart, but the underlying mechanism remains poorly understood.<h4>Methods</h4>To gain insights on primary effects of SGLT2i that are not confounded by pathophysiologic processes or are secondary to improvement by SGLT2i, we performed an in-depth proteomics, phosphoproteomics, and metabolomics analysis by integrating signatures from multiple metabolic organs and body fluids after 1 week of SG ...[more]

PMID: 38152989

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