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AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis, which coordinates metabolic pathways and thus balances nutrient supply with energy demand. Because of the favorable physiological outcomes of AMPK activation on metabolism, AMPK has been considered to be an important therapeutic target for controlling human diseases including metabolic syndrome and cancer. Thus, activators of AMPK may have potential as novel therapeutics for these diseases. In this review, we provide a comprehensive summary of both indirect and direct AMPK activators and their modes of action in relation to the structure of AMPK. We discuss the functional differences among isoform-specific AMPK complexes and their significance regarding the development of novel AMPK activators and the potential for combining different AMPK activators in the treatment of human disease.
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http://dx.doi.org/10.1038/emm.2016.16 | DOI Listing |
Bioorg Med Chem Lett
September 2025
Galapagos SASU, 102 avenue Gaston Roussel, 93230 Romainville, France. Electronic address:
The salt-inducible kinase (SIK) family encompasses three isoforms, SIK1, SIK2, and SIK3, which are members of the AMP-activated protein kinase (AMPK) family of serine/threonine protein kinases. SIK inhibition has emerged as a potential therapeutic approach across multiple indications, as SIKs regulate a diverse set of physiological processes such as metabolism, bone remodeling, immune response, malignancies, skin pigmentation, and circadian rhythm. Within isoform-specific SIK inhibitors there is a need to understand the distinct role of each protein, and here we describe the first SIK1 selective inhibitors.
View Article and Find Full Text PDFJ Ethnopharmacol
September 2025
Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address:
Ethnopharmacological Relevance: Acute lung injury (ALI) is a severe health issue characterized by high morbidity and mortality, driven by excessive inflammatory responses. The traditional Chinese medicine Huashi Baidu Granules (HBG) demonstrated clinical efficacy in treating severe ALI, yet its mechanisms remain unclear.
Aim Of The Study: This research aimed to examine the efficacy and underlying mechanisms of HBG in a lipopolysaccharide (LPS)-induced ALI model, identify core herbal constituents, active compounds, and therapeutic targets, providing a foundation for optimizing HBG-based treatments.
Exp Physiol
September 2025
Department of Hepatobiliary Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, China.
Hepatic ischaemia-reperfusion (IR) injury is a serious clinical issue, especially in patients with type 2 diabetes mellitus (T2DM). As mitochondria play a critical role in the regulation of IR-induced liver damage, mitochondria-targeted treatment is of the utmost significance for improving outcomes. The present study explored the mitoprotective role of combined ginsenoside-MC1 (GMC1) and irisin administration in diabetic rats with hepatic IR injury.
View Article and Find Full Text PDFJ Agric Food Chem
September 2025
Center of Drug Safety Evaluation, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
Creating effective treatments for type 2 diabetes mellitus (T2DM) remains a critical global health challenge. This study investigates the antidiabetic mechanisms of subsp. B-53 ( B-53) in T2DM mice.
View Article and Find Full Text PDFInt J Mol Med
November 2025
Department of Neurosciences 'Rita Levi Montalcini', University of Turin, I‑10125 Turin, Italy.
Kinases are activators of well‑known inflammatory cascades implicated in metabolic disorders, and abnormal activation of casein kinase II (CK2) is associated with several inflammatory disorders. However, thus far, its role in the low‑grade chronic inflammatory response known as 'metaflammation', which is a hallmark of obesity and type 2 diabetes, has not yet been elucidated. The present study aimed to evaluate the role of CK2 in diet‑induced metaflammation and the effects of the CK2 inhibitor 4,5,6,7‑tetrabromobenzotriazole (TBB) on a murine model fed a high‑fat‑high‑sugar (HFHS) diet.
View Article and Find Full Text PDF