Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a key treatment for type 2 diabetes mellitus (T2DM), with cardiorenal effects that extend beyond glycemic management. One important mechanism und Show more
Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a key treatment for type 2 diabetes mellitus (T2DM), with cardiorenal effects that extend beyond glycemic management. One important mechanism underpinning these pleiotropic effects is their interaction with AMP-activated protein kinase (AMPK), a crucial regulator of cellular energy balance. This review summarizes the strong evidence that SGLT2 inhibitors activate AMPK via both shared and drug-specific mechanisms. Empagliflozin induces on-target energetic stress, dapagliflozin activates the FGFR1-LKB1 axis, and canagliflozin inhibits mitochondrial complex I off-target. We describe how AMPK activation coordinates a protective network that includes PGC-1α-mediated mitochondrial biogenesis, ULK1-driven autophagy, Nrf2-antioxidant responses, and mTOR/NF-κB signaling inhibition. This interaction leads to enhanced insulin sensitivity, decreased oxidative stress, and sustained heart, kidney, and liver function. Furthermore, we conduct a comparative investigation of the distinct AMPK-modulatory profiles of prominent SGLT2 inhibitors and explore the practical applicability of these processes, including possible drawbacks such as the theoretical risk of muscle atrophy associated with persistent AMPK activation. By thoroughly describing the SGLT2-AMPK axis, this review emphasizes its importance as a therapeutic target and offers a framework for understanding the entire range of SGLT2 inhibitor activity in diabetes and associated consequences. Show less
Transformation of macrophages to foam cells is determined by the rates of cholesterol uptake and efflux. This study uses a real time RT-PCR technique to investigate the role of conjugated linoleic aci Show more
Transformation of macrophages to foam cells is determined by the rates of cholesterol uptake and efflux. This study uses a real time RT-PCR technique to investigate the role of conjugated linoleic acid (CLA), α-linolenic acid (ALA) and eicosapentaenoic acid (EPA) in the regulation of the ATP-binding cassette A1 (ABCA1) and liver X receptor α (LXR) genes, which are involved in cholesterol homeostasis. Accordingly, these fatty acids significantly reduced the total, free and esterified cholesterols within the foam cells. While the expression of the ABCA1 and LXRα genes was increased in the presence of the pharmacological LXRα ligand, T0901317, their mRNA expression was not significantly affected by CLA, ALA and EPA. These results suggest that although polyunsaturated fatty acids have an effect on cholesterol homeostasis, they cannot change the expression of the ABCA1 and LXRα genes. Alternatively, several other genes and proteins may be involved. Show less