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Beyond ketosis: the search for the mechanism underlying SGLT2-inhibitor benefit continues.
J Clin Invest
December 2024
Division of Nutritional Science and Obesity Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Despite the impressive clinical benefits and widespread adoption of sodium glucose cotransporter 2 inhibitors (SGLT2i) to treat all classes of heart failure, their cardiovascular mechanisms of action are poorly understood. Proposed mechanisms range broadly and include enhanced ketogenesis, where the mild ketosis associated with SGLT2i use is presumed to be beneficial. However, in this issue of the JCI, carefully conducted metabolic flux studies by Goedeke et al.
View Article and Find Full Text PDFSGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts.
J Clin Invest
December 2024
Department of Internal Medicine (Endocrinology), Yale School of Medicine, New Haven Connecticut, USA.
Previous studies highlight the potential for sodium-glucose cotransporter type 2 (SGLT2) inhibitors (SGLT2i) to exert cardioprotective effects in heart failure by increasing plasma ketones and shifting myocardial fuel utilization toward ketone oxidation. However, SGLT2i have multiple in vivo effects and the differential impact of SGLT2i treatment and ketone supplementation on cardiac metabolism remains unclear. Here, using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology combined with infusions of [13C6]glucose or [13C4]βOHB, we demonstrate that acute SGLT2 inhibition with dapagliflozin shifts relative rates of myocardial mitochondrial metabolism toward ketone oxidation, decreasing pyruvate oxidation with little effect on fatty acid oxidation in awake rats.
View Article and Find Full Text PDFThe Effects of SGLT2 Inhibitors on Blood Pressure and Other Cardiometabolic Risk Factors.
Int J Mol Sci
November 2024
Center for Nephrology "G. Papadakis", General Hospital of Nikaia-Piraeus "Ag. Panteleimon", 18454 Nikaia, Greece.
Article Synopsis
- - SGLT2 inhibitors not only help with blood sugar, heart health, and kidney protection but also influence blood pressure, body weight, and fat metabolism.
- - Blood pressure decreases can vary based on individual health history, with modest drops in body weight (1-2 kg) mainly due to fat loss from excess sugar and calorie loss.
- - Changes in lipid levels include slight reductions in triglycerides and increases in both HDL and LDL cholesterol, but the exact reasons behind these effects are still being researched.
Sodium glucose cotransporter 2 inhibitors in the management of heart failure: Veni, Vidi, and Vici.
World J Cardiol
October 2024
Department of Cardiology, King Georg's Medical University, Lucknow 226003, Uttar Pradesh, India.
Heart failure (HF) is a chronic disease associated with high morbidity and mortality rates. Renin-angiotensin-aldosterone system blockers (including angiotensin receptor/neprilysin inhibitors), beta-blockers, and mineralocorticoid receptor blockers remain the mainstay of pharmacotherapy for HF with reduced ejection fraction (HFrEF). However, despite the use of guideline-directed medical therapy, the mortality from HFrEF remains high.
View Article and Find Full Text PDFThe effects of sodium-glucose cotransporter 2 inhibitors on the 'forgotten' right ventricle.
ESC Heart Fail
October 2024
Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Article Synopsis
- Advances in diagnosis and treatment have highlighted how impaired right ventricular (RV) function significantly impacts heart failure prognosis, regardless of left ventricular ejection fraction.
- Right heart failure (RHF) can arise from multiple conditions, such as congenital heart disease and pulmonary arterial hypertension, and may occur after left ventricular assist devices are used.
- Recent studies focus on the use of SGLT2 inhibitors, particularly gliflozins, in improving RV function by addressing issues like RV overload and inflammation, while also discussing their implications for future clinical approaches and research.
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