bims-sikglu Biomed News
on Salt inducible kinases in glucose metabolism
Issue of 2025–02–02
two papers selected by
Dipsikha Biswas, Københavns Universitet and Maria Madrazo i Montoya, Københavns Universitet
  1. Small Molecule Modulators of AMP-Activated Protein Kinase (AMPK) Activity and Their Potential in Cancer Therapy.
  2. An insight on the additive impact of type 2 diabetes mellitus and nonalcoholic fatty liver disease on cardiovascular consequences.
  1. J Med Chem. 2025 Jan 29.
    Small Molecule Modulators of AMP-Activated Protein Kinase (AMPK) Activity and Their Potential in Cancer Therapy.
    Juliet E Strang, Daniel D Astridge, Vu T Nguyen, Philip Reigan.
      AMP-activated protein kinase (AMPK) is a central mediator of cellular metabolism and is activated in direct response to low ATP levels. Activated AMPK inhibits anabolic pathways and promotes catabolic activities that generate ATP through the phosphorylation of multiple target substrates. AMPK is a therapeutic target for activation in several chronic metabolic diseases, and there is increasing interest in targeting AMPK activity in cancer where it can act as a tumor suppressor or conversely it can support cancer cell survival. Small molecule AMPK activators and inhibitors have demonstrated some success in suppressing cancer growth, survival, and drug resistance in preclinical cancer models. In this perspective, we summarize the role of AMPK in cancer and drug resistance, the influence of the tumor microenvironment on AMPK activity, and AMPK activator and inhibitor development. In addition, we discuss the potential importance of isoform-selective targeting of AMPK and approaches for selective AMPK targeting in cancer.
    DOI:  https://doi.org/10.1021/acs.jmedchem.4c02354
  2. Mol Biol Rep. 2025 Jan 28. 52(1): 169
    An insight on the additive impact of type 2 diabetes mellitus and nonalcoholic fatty liver disease on cardiovascular consequences.
    Monika Bhardwaj, Papiya Mitra Mazumder.
       BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are associated with a multifactorial complicated aetiology that is often coexisting and has a strong and distinct connection with cardiovascular diseases (CVDs). In order to accomplish effective and appropriate therapeutic strategies, a deeper understanding of the bidirectional interaction between NAFLD patients, NAFLD patients with T2DM, and NAFLD patients with CVDs is required to control the concomitant rise in prevalence of these conditions worldwide. This article also aims to shed light on the epidemiology and mechanisms behind the relationship between T2DM, NAFLD and the related cardiovascular consequences.
    METHOD: Literature was collected from PubMed, Medline, Embase, Web of Science and Google scholar from inception to June, 2024. For surveying literature different combinations and formats of terms including NAFLD, NASH, T2DM and CVDs were used.
    RESULTS: In the recent decade, clinical and epidemiological studies have been conducted and provide strong evidence that NAFLD is closely linked with CVD progression along with associated morbidity and mortality in both patients with and without T2DM. Several mechanistic approaches contribute to cardiovascular consequences and abnormalities in cardiac biomarkers in T2DM and NAFLD patients, including adipose tissue malfunction, mitochondrial dysfunction, the microbiota, genetic and epigenetic alterations contributing to insulin resistance, glucotoxicity and lipotoxicity.
    CONCLUSION: The study reveals a complex interplay between diabetes, hepatic and cardiovascular complications, leading to significant morbidity and mortality in diabetic and NAFLD patients. This pandemic necessitates further research to identify mitigating variables and develop effective treatment approaches.
    Keywords:  Cardiovascular diseases; Mechanism of coexistence; Metabolic syndrome; Nonalcoholic fatty liver disease; Type 2 diabetes mellitus
    DOI:  https://doi.org/10.1007/s11033-025-10249-0
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