Canagliflozin regulates metabolic reprogramming in diabetic kidney disease by inducing fasting-like and aestivation-like metabolic patterns

Diabetologia, Год журнала: 2024, Номер 67(4), С. 738 - 754

Опубликована: Янв. 18, 2024

Язык: Английский

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Inflammatory Trajectory of Type 2 Diabetes: Novel Opportunities for Early and Late Treatment

Cells, Год журнала: 2024, Номер 13(19), С. 1662 - 1662

Опубликована: Окт. 8, 2024

Low-grade inflammation (LGI) represents a key driver of type 2 diabetes (T2D) and its associated cardiovascular diseases (CVDs). Indeed, inflammatory markers such as hs-CRP IL-6 predict the development T2D complications, suggesting that LGI already increases before diagnosis remains elevated even after treatment. Overnutrition, unhealthy diets, physical inactivity, obesity, aging are all recognized triggers LGI, promoting insulin resistance sustaining pathogenesis T2D. Once developed, frank appearance, people with undergo pathological metabolic remodeling, an alteration multiple CVD risk factors, i.e., glycemia, lipids, blood pressure, renal function. In turn, variables foster range pathways mechanisms, e.g., immune cell stimulation, accrual senescent cells, long-lasting epigenetic changes, trained immunity, which held to chronically fuel at systemic tissue levels. Targeting factors partially ameliorates LGI. However, some unaffected by common therapies, burden is still increased in many patients, phenomenon possibly underlying residual (i.e., having > mg/dL despite optimal LDL cholesterol control). On other hand, selected disease-modifying drugs, GLP-1RA, seem also act on T2D, curbing trajectory disease preventing it if introduced early. addition, trials demonstrated potential canonical anti-inflammatory therapies reducing rate CVDs patients this condition or high for it, whom had Since colchicine, inhibitor activation, now approved prevention CVDs, might be worth exploring possible therapeutic paradigm identify subjects treat them drug. Upcoming studies will reveal whether drugs reverse early suppressing sources colchicine has broad benefit condition.

Язык: Английский

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Cellular and Mitochondrial Pathways Contribute to SGLT2 Inhibitors-mediated Tissue Protection: Experimental and Clinical Data

Current Pharmaceutical Design, Год журнала: 2024, Номер 30(13), С. 969 - 974

Опубликована: Март 29, 2024

Abstract: In metabolic syndrome and diabetes, compromised mitochondrial function emerges as a critical driver of cardiovascular disease, fueling its development persistence, culminating in cardiac remodeling adverse events. this context, angiotensin II - the main interlocutor renin-angiotensin-aldosterone system promotes local systemic oxidative inflammatory processes. To highlight, low activity/expression proteins called sirtuins negatively participates these processes, allowing more significant imbalance, which impacts cellular tissue responses, causing damage, inflammation, vascular remodeling. The reduction energy production mitochondria has been widely described element all types disorders. Additionally, high sirtuin levels AMPK signaling stimulate hypoxia-inducible factor 1 beta promote ketonemia. Consequently, enhanced autophagy mitophagy advance through cells, sweeping away debris silencing orchestra stress ultimately protecting vulnerable from damage. highlight particular interest, SGLT2 inhibitors (SGLT2i) profoundly influence mechanisms. Randomized clinical trials have evidenced compelling picture SGLT2i emerging game-changers, wielding their power to demonstrably improve slash rates renal Furthermore, driven by recent evidence, emerge supermolecules, exerting beneficial actions increase efficiency, alleviate stress, curb severe inflammation. Its strengthen tissues create resilient defense against disease. conclusion, like treasure chest brimming with untold riches, on holds potential for health. Unlocking secrets, map guiding adventurers hidden promises pave way even potent therapeutic strategies.

Язык: Английский

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Duality of Branched-Chain Amino Acids in Chronic Cardiovascular Disease: Potential Biomarkers versus Active Pathophysiological Promoters

Nutrients, Год журнала: 2024, Номер 16(12), С. 1972 - 1972

Опубликована: Июнь 20, 2024

Branched-chain amino acids (BCAAs), comprising leucine (Leu), isoleucine (Ile), and valine (Val), are essential nutrients vital for protein synthesis metabolic regulation via specialized signaling networks. Their association with cardiovascular diseases (CVDs) has become a focal point of scientific debate, emerging evidence suggesting both beneficial detrimental roles. This review aims to dissect the multifaceted relationship between BCAAs health, exploring molecular mechanisms clinical implications. Elevated BCAA levels have also been linked insulin resistance (IR), type 2 diabetes mellitus (T2DM), inflammation, dyslipidemia, which well-established risk factors CVD. Central these processes key pathways such as mammalian target rapamycin (mTOR) signaling, nuclear factor kappa-light-chain-enhancer activate B cells (NF-κB)-mediated oxidative stress. Additionally, interplay metabolism gut microbiota, particularly production metabolites like trimethylamine-N-oxide (TMAO), adds another layer complexity. Contrarily, some studies propose that may cardioprotective effects under certain conditions, contributing muscle maintenance health. critically evaluates evidence, addressing biological basis signal transduction mechanism, discusses potential act biomarkers versus active mediators pathology. By presenting balanced analysis, this seeks clarify contentious roles in CVD, providing foundation future research therapeutic strategies required because rising prevalence, incidence, total burden CVDs.

Язык: Английский

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Dapagliflozin Attenuates Diabetes-Induced Podocyte Lipotoxicity via ERRα-Mediated Lipid Metabolism

Free Radical Biology and Medicine, Год журнала: 2025, Номер 234, С. 178 - 191

Опубликована: Апрель 19, 2025

Язык: Английский

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Risk of colorectal cancer and cancer‐related mortality in type 2 diabetes patients treated with metformin, SGLT‐2 inhibitors, or their combination

Cancer Communications, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Язык: Английский

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Mechanisms of heart failure and chronic kidney disease protection by SGLT2 inhibitors in nondiabetic conditions

AJP Cell Physiology, Год журнала: 2024, Номер 327(3), С. C525 - C544

Опубликована: Июнь 17, 2024

Sodium-glucose cotransporter 2 inhibitors (SGLT2is), initially developed for type diabetes (T2D) treatment, have demonstrated significant cardiovascular and renal benefits in heart failure (HF) chronic kidney disease (CKD), irrespective of T2D. This review provides an analysis the multifaceted mechanisms underlying cardiorenal SGLT2i HF CKD outside T2D context. Eight major aspects protective effects beyond glycemic control are explored:

Язык: Английский

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Management of type 2 diabetes in patients with compensated liver cirrhosis: Short of evidence, plenty of potential

Diabetes & Metabolic Syndrome Clinical Research & Reviews, Год журнала: 2023, Номер 18(1), С. 102935 - 102935

Опубликована: Дек. 28, 2023

Язык: Английский

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Redox-driven cardioprotective effects of sodium-glucose co-transporter-2 inhibitors: comparative review

Cardiovascular Diabetology, Год журнала: 2023, Номер 22(1)

Опубликована: Апрель 29, 2023

Sodium-glucose co-transporter-2 inhibitors are used in the treatment of diabetes but also emerging as cardioprotective agents heart diseases even absence type 2 diabetes. In this paper, upon providing a short overview common pathophysiological features diabetes, we review clinically reported cardio- and nephroprotective potential sodium-glucose currently available on market, including Dapagliflozin, Canagliflozin, Empagliflozin. To that end, summarize findings clinical trials have initially drawn attention to drugs' organ-protective potential, before an their proposed mechanism action. Since particularly expect antioxidative properties will broaden application gliflozins from therapeutic preventive care, special emphasis was put aspect.

Язык: Английский

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Nascent shifts in renal cellular metabolism, structure, and function due to chronic empagliflozin in prediabetic mice

AJP Cell Physiology, Год журнала: 2024, Номер 326(4), С. C1272 - C1290

Опубликована: Март 4, 2024

Sodium-glucose cotransporter, type 2 inhibitors (SGLT2i) are emerging as the gold standard for treatment of diabetes (T2D) with renal protective benefits independent glucose lowering. We took a high-level approach to evaluate effects SGLT2i, empagliflozin (EMPA) on metabolism and function in prediabetic model metabolic syndrome. Male female 12-wk-old TallyHo (TH) mice, their closest genetic lean strain (Swiss-Webster, SW) were treated high-milk-fat diet (HMFD) plus/minus EMPA (@0.01%) 12-wk. Kidney weights glomerular filtration rate slightly increased by TH mice. Glomerular feature analysis unsupervised clustering revealed sexually dimorphic clustering, one unique cluster relating EMPA. Periodic acid Schiff (PAS) positive areas, reflecting basement membranes mesangium reduced Phasor-fluorescent life-time imaging (FLIM) free-to-protein bound NADH cortex showed marginally greater reliance oxidative phosphorylation Overall, net urine sodium, glucose, albumin In TH, sodium phosphate (NaPi-2), but hydrogen exchanger, 3 (NHE3). These changes absent or blunted SW. led exosomal microRNA profile including, females, enhanced levels miRs 27a-3p, 190a-5p, 196b-5p. Network "cancer pathways" "FOXO signaling" major regulated pathways. mice limited disease resulted modifications metabolism, structure, transport, which may preclude underlie protection against kidney developing T2D.

Язык: Английский

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