SGLT2 inhibitors and AMPK: The road to cellular housekeeping?

Hamid Reza Nejabati, Ziba Majidi, Nasser Safaie, Yousef Faridvand, Shaban Alizadeh, Shahab Masoumi, Pourya Mirzajanzadeh, Mobasher Hajiabbasi, Vahid Alivirdiloo, Neda Chobdari Basmenji, Aysan Derakhshi Radvar

Journal: Cell biochemistry and function 2024;42(1):e3922

PMID: 38269506

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Abstract

Sodium-glucose co-transporter-2 (SGLT2) inhibitors, known as Gliflozins, are a class of Glucose-lowering drugs in adults with type 2 diabetes (T2D) that induce glucosuria by blocking SGLT2 co-transporters in the proximal tubules. Several lines of evidence suggest that SGLT2 inhibitors regulate multiple mechanisms associated with the regulation of varying cellular pathways. The 5'-adenosine monophosphate-activated protein kinase (AMPK) pathway plays an important role in metabolic homeostasis by influencing cellular processes. Recently, it has been shown that SGLT2 inhibitors can affect the AMPK pathway in differing physiological and pathological ways, resulting in kidney, intestinal, cardiovascular, and liver protective effects. Additionally, they have therapeutic effects on nonalcoholic fatty liver disease and diabetes mellitus-associated complications. In this review, we summarize the results of studies of AMPK-associated therapeutic effects of SGLT2 inhibitors in different organelle functions.

Address: Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.; Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.; Cardiovascular Fellowship, Vanderbilt University of Medical center, Nashville, Tennessee, USA.; Department of Hematology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.; Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.; Faculty of Medicine, Islamic Azad University of Tonekabon, Tonekabon, Iran.; Ramsar Campus, Mazandaran University of Medical Sciences, Ramasr, Iran.; Department of Medical Laboratory Science, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.; Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.

DOI: 10.1002/cbf.3922

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MeSH Terms: Adult, Humans, AMP-Activated Protein Kinases, Sodium-Glucose Transporter 2 Inhibitors, Diabetes Mellitus, Type 2, Sodium-Glucose Transporter 2, Glucose, Household Work