SGLT2i and GLP1-RA exert additive cardiorenal protection with a RAS blocker in uninephrectomized db/db mice DOI Creative Commons

Nerea Martos-Guillami,

Ander Vergara, Carmen Llorens-Cebrià

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 7, 2024

Introduction Diabetic Kidney Disease (DKD) is the main cause of end-stage renal disease in developed world. The current treatment DKD with renin-angiotensin system (RAS) blockade does not totally halt progression to end stage kidney disease. Currently, several drugs have shown delay such as sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like-1 receptor agonists (GLP-1RA). We hypothesized that by combining prevent on top RAS a synergistic effect would be achieved terms cardiorenal protection. In present study, we analysed if combination blocker (ramipril) SGLT2i (empagliflozin) and/or GLP-1RA (semaglutide) type 2 diabetic mouse model could add-on effects heart Methods Male female uninephrectomized db/db mice were treated empagliflozin semaglutide ramipril during 8 weeks. During study body weight, water food intake weekly monitored, glycaemia biweekly albuminuria glomerular filtration rate (GFR) before after treatment. At experiment, isolated for histological gene expression studies well intrarenal state assessment. Results Semaglutide combined significantly decreased but only when both compounds, further blood glucose, hyperfiltration male mesangial matrix expansion. kidney, triple empagliflozin, reduced proinflammatory profibrotic genes ccl2 TGFß1. addition, was superior decreasing cardiomyocyte hypertrophy fibrosis mice. Discussion Our results suggest protection than administered alone blockade.

Language: Английский

The effects of Fc fusion protein glucagon-like peptide-1 and glucagon dual receptor agonist with different receptor selectivity in vivo studies DOI Open Access
Peng Jiang, Ying Zeng,

Wen Yang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116485 - 116485

Published: March 22, 2024

Glucagon-like peptide-1 (GLP-1)/glucagon (GCG) dual receptor agonists with different selectivity are under investigation and have shown significant improvement in both weight loss glycemic control, but the optimal potency ratio between two receptors to balance efficacy safety remains unclear. We designed constructed several ratios using Fc fusion protein technology. The long-term effects of candidates on body metabolic dysfunction-associated steatotic liver disease (MASLD) were evaluated diet-induced obese (DIO) model mice, high-fat diet (HFD)-ob/ob mice AMLN MASLD mice. Repeat dose toxicity assays performed investigate profile candidate (HEC-C070) Sprague Dawley (SD) rats. high GCG (GCGR) HEC-C046 makes it more prominent than other compounds for most parameters may lead concerns. change HEC-C052 lowest agonism was inferior that selective GLP-1 agonist (GLP-1RA) semaglutide DIO GLP-1R HEC-C070 moderate has a effect function its observed adverse level (LOAEL) 30 nmol/kg repeat study. compared potential GLP-1/GCG provide setting future treat obesity MASLD.

Language: Английский

Citations

2
Peptide GLP-1 receptor agonists: From injection to oral delivery strategies DOI

Zhiqiang Ke,

Qianqian Ma,

Xiaonan Ye

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 229, P. 116471 - 116471

Published: Aug. 8, 2024

Language: Английский

Citations

1
SGLT2i and GLP1-RA exert additive cardiorenal protection with a RAS blocker in uninephrectomized db/db mice DOI Creative Commons

Nerea Martos-Guillami,

Ander Vergara, Carmen Llorens-Cebrià

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 7, 2024

Introduction Diabetic Kidney Disease (DKD) is the main cause of end-stage renal disease in developed world. The current treatment DKD with renin-angiotensin system (RAS) blockade does not totally halt progression to end stage kidney disease. Currently, several drugs have shown delay such as sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like-1 receptor agonists (GLP-1RA). We hypothesized that by combining prevent on top RAS a synergistic effect would be achieved terms cardiorenal protection. In present study, we analysed if combination blocker (ramipril) SGLT2i (empagliflozin) and/or GLP-1RA (semaglutide) type 2 diabetic mouse model could add-on effects heart Methods Male female uninephrectomized db/db mice were treated empagliflozin semaglutide ramipril during 8 weeks. During study body weight, water food intake weekly monitored, glycaemia biweekly albuminuria glomerular filtration rate (GFR) before after treatment. At experiment, isolated for histological gene expression studies well intrarenal state assessment. Results Semaglutide combined significantly decreased but only when both compounds, further blood glucose, hyperfiltration male mesangial matrix expansion. kidney, triple empagliflozin, reduced proinflammatory profibrotic genes ccl2 TGFß1. addition, was superior decreasing cardiomyocyte hypertrophy fibrosis mice. Discussion Our results suggest protection than administered alone blockade.

Language: Английский

Citations

0