- |||||||||| metformin / Generic mfg.
Journal: A Fbxo48 inhibitor prevents pAMPKα degradation and ameliorates insulin resistance. (Pubmed Central) - Apr 7, 2021 We have generated a novel Fbxo48 inhibitory compound, BC1618, whose potency in stimulating Ampk-dependent signaling greatly exceeds 5-aminoimidazole-4-carboxamide-1-β-ribofuranoside (AICAR) or metformin...Hence, we provide a unique bioactive compound that inhibits pAmpkα disposal. Together, these results define a new pathway regulating Ampk biological activity and demonstrate the potential utility of modulating this pathway for therapeutic benefit.
- |||||||||| sirolimus / Generic mfg.
Journal: AMPK and Akt/mTOR signaling pathways participate in glucose-mediated regulation of HBV replication and cellular autophagy. (Pubmed Central) - Mar 23, 2021 mTOR inhibition by rapamycin reversed negative effects of high glucose concentrations on HBV replication, suggesting that low glucose concentration promotes HBV replication by stimulating the AMPK/mTOR-ULK1-autophagy axis...Surprisingly, the glucose analogue 2-deoxy-D-glucose (2-DG), reduced HBV replication through activating the Akt/mTOR signaling pathway, also at the low glucose concentrations. Our study reveals that glucose is an important factor for the HBV life cycle by regulating HBV transcription and posttranscriptional steps of HBV replication via cellular autophagy.
- |||||||||| metformin / Generic mfg., temozolomide / Generic mfg.
Journal: Cetylpyridinium chloride is a potent AMP-activated kinase (AMPK) inducer and has therapeutic potential in cancer. (Pubmed Central) - Feb 24, 2021 Mitochondrial biogenesis and bioenergetics changes have also been implicated in glioblastoma, which is the most aggressive form of brain tumors. Cetylpyridinium chloride has been administered in humans as a safe drug-disinfectant for several decades, and we report here that under in vitro conditions, cetylpyridinium chloride kills glioblastoma cells in a dose dependent manner at a higher efficacy compared to current standard of care drug, temozolomide.
- |||||||||| Journal: Mechanisms by which adiponectin reverses high fat diet-induced insulin resistance in mice. (Pubmed Central) - Feb 20, 2021
These data suggest that adiponectin and adiponectin-related molecules reverse lipid-induced liver and muscle insulin resistance by reducing ectopic lipid storage in these organs, resulting in decreased plasma membrane sn-1,2-DAG-induced nPKC activity and increased insulin signaling. Adiponectin mediates these effects by both promoting the storage of TAG in eWAT likely through stimulation of LPL as well as by stimulation of AMPK in muscle resulting in increased muscle fat oxidation.
- |||||||||| [VIRTUAL] AMPK stimulates insulin clearance in hepatocytes (Room 3) - Jan 6, 2021 - Abstract #WSMRF2021WSMRF_390;
Our results also suggest that AMPK activation may increase the rate of INSR recycling back to the cell surface. In conclusion, our study raises the possibility that the modulation of insulin clearance via AMPK may offer a novel therapeutic approach in the prevention or treatment of T2D.
- |||||||||| Journal: The ULK1/2 and AMPK Inhibitor SBI-0206965 Blocks AICAR and Insulin-Stimulated Glucose Transport. (Pubmed Central) - Jan 6, 2021
As insulin is known to neither activate AMPK nor require AMPK to stimulate glucose transport, and insulin inhibits ULK1/2 activity, these data strongly suggest that SBI-0206965 has a non-specific off-target inhibitory effect on muscle glucose transport. Thus, SBI-0206965 is not a specific inhibitor of the AMPK/ULK-signaling axis in skeletal muscle, and data generated with this inhibitor must be interpreted with caution.
- |||||||||| selisistat (SEN-196) / AOP Orphan Pharma
Journal: Anti-insulin resistance effects of salidroside through mitochondrial quality control. (Pubmed Central) - Sep 21, 2020 Blood levels of glucose and insulin as well as cellular glucose uptake were determined, and mitochondrial function and MQC-associated parameters and reactive oxygen species (ROS) production were analyzed based on treatments with the activator (AICAR), inhibitors (compound C and EX-527) or specific siRNA of Ampk/Sirt1 and mitochondrial ROS scavenger (mito-TEMPO)...Since IR is a critical issue for public health, to explore a potent agent against IR is of high interest. The anti-IR effects of salidroside warrant further experimental and clinical studies.
- |||||||||| Preclinical, Journal: Bouchardatine analogue alleviates NAFLD/NASH in high fat fed mice via blunting ATP synthase activity. (Pubmed Central) - Sep 9, 2020
Neo-adjuvant metformin and TMZ followed by concurrent TMZ/metformin and HART and adjuvant TMZ/metformin is feasible and safe, and the results compare favorably to current GBM literature, especially for patients with unmethylated MGMT. R17 has a therapeutic potential for NAFLD/NASH and its molecular mode of action involves the elimination of ER and oxidative stresses possibly via activating the LKB1-AMPK axis by blunting the activity of ATP synthase.
- |||||||||| Journal, IO Biomarker: Choline Uptake and Metabolism Modulate Macrophage IL-1β and IL-18 Production. (Pubmed Central) - Aug 15, 2020
By potentiating mitochondrial recruitment of DRP1, AMPK stimulates mitophagy, which contributes to termination of NLRP3 inflammasome activation. Correspondingly, choline kinase inhibitors ameliorated acute and chronic models of IL-1β-dependent inflammation.
- |||||||||| Review, Journal: Protective effects of glycycoumarin on liver diseases. (Pubmed Central) - Aug 2, 2020
Recent studies by us demonstrated that GCM is highly effective against alcoholic liver disease, nonalcoholic fatty liver disease, acetaminophen-induced hepatotoxicity, and liver cancer through mechanisms involved in activation of Nrf2 antioxidant system, stimulation of AMPK-mediated energy homeostasis, induction of autophagy degradation process, and inhibiting oncogenic kinase T-lymphokine-activated killer cell-originated protein kinase activity. In this review, we summarize the findings on the hepatoprotective effect of GCM, discuss the signaling pathways underlying GCM-induced protective effect on liver diseases, and propose the issues that need to be addressed to promote further development of GCM as a clinically useful hepatoprotective agent.
- |||||||||| Journal: Membrane raft-mediated regulation of glucose signaling pathway leading to acrosome reaction in chicken sperm. (Pubmed Central) - Jun 12, 2020
To better understand the mechanism of AMPK activation by glucose, we evaluated localization and phosphorylation status of AMPKα, showing that glucose uptake stimulates AMPKα phosphorylation, leading to its complete activation. Together, these results lead us to propose a novel mechanism by which glucose uptake stimulates the AMPK signaling pathway via membrane rafts, resulting in maximal acrosomal responsiveness in avian sperm as migrating upward to a fertilization site.
- |||||||||| Journal, Myeloid-derived suppressor cells, IO Biomarker: AMPK alpha-1 intrinsically regulates the function and differentiation of tumor myeloid-derived suppressor cells. (Pubmed Central) - May 31, 2020
In addition, Prkaa1 deletion antagonized the differentiation of monocytic-MDSC (M-MDSC) to macrophages, and re-routed M-MDSC, but not granulocytic-MDSC (PMN-MDSC), into cells that elicited direct anti-tumor cytotoxic effects through nitric oxide synthase 2 (Nos2)-mediated actions. Thus, our results demonstrate the primary role of AMPK alpha-1 in the immunosuppressive effects induced by tumor-MDSC, and support the therapeutic use of AMPK-inhibitors to overcome MDSC-induced T-cell dysfunction in cancer.
- |||||||||| sirolimus / Generic mfg.
Journal: Folliculin Interacting Protein 1 Maintains Metabolic Homeostasis during B Cell Development by Modulating AMPK, mTORC1, and TFE3. (Pubmed Central) - May 28, 2020 In response to low energy, AMPK stimulates catabolic pathways such as autophagy to enhance energy production while inhibiting anabolic pathways regulated by the mechanistic target of rapamycin complex 1 (mTORC1)...Fnip1-deficient B cell progenitors exhibited increased nuclear localization of transcription factor binding to IgHM enhancer 3 (TFE3) in developing B cells, which correlated with an increased expression of TFE3-target genes, increased lysosome numbers and function, and increased autophagic flux. These results indicate that Fnip1 modulates autophagy and energy response pathways in part through the regulation of AMPK, mTORC1, and TFE3 in B cell progenitors.
- |||||||||| metformin / Generic mfg., sirolimus / Generic mfg., University of Cincinnati
Preclinical, Journal: Indirect AMPK activators prevent incision-induced hyperalgesia and block hyperalgesic priming while positive allosteric modulators only block priming in mice. (Pubmed Central) - Apr 22, 2020 AMPK can be activated directly using positive allosteric modulators, as well as indirectly through the upregulation of upstream kinases, such as liver kinase B1 (LKB1), which is a mechanism of action of metformin...We conclude that indirect AMPK activators are likely to be more effective as potential therapeutics for post-surgical pain because they inhibit acute pain caused by incision and also prevent long-term neuronal plasticity that is involved in persistent post-surgical pain. Our work points to the natural product, indirect AMPK activator, narciclasine, as an excellent starting point for development of therapeutics.
- |||||||||| Journal: Propionate suppresses hepatic gluconeogenesis via GPR43/AMPK signaling pathway. (Pubmed Central) - Mar 24, 2020
Thus, our data indicate that the binding of propionate to hepatic GPR43 elicits CaMKKβ-dependent activation of AMPK through intracellular Ca increase, leading to suppression of gluconeogenesis. The present study suggests the potential efficacy of propionate in preventive and therapeutic management of diabetes.
- |||||||||| cisplatin / Generic Mfg.
Journal: Histone deacetylase inhibitors protect against cisplatin-induced acute kidney injury by activating autophagy in proximal tubular cells. (Pubmed Central) - Nov 28, 2019 Here we demonstrate that two widely tested HDACi (suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA)) protect the kidneys in cisplatin-induced AKI by enhancing autophagy...Notably, inhibition of autophagy by chloroquine or by autophagy gene 7 (Atg7) ablation diminished the protective effect of TSA...Mechanistically, TSA stimulated AMPK and inactivated mTOR during cisplatin treatment of proximal tubule cells and kidneys in mice. Together, these results suggest that HDACi may protect kidneys by activating autophagy in proximal tubular cells.
- |||||||||| metformin / generics
Preclinical, Journal: Role of PKC and AMPK in hypertonicity-stimulated water reabsorption in rat inner medullary collecting ducts. (Pubmed Central) - Nov 28, 2019 When inner medullary tissue was treated with the PKC activator phorbol dibutyrate (PDBu), the AMPK activator metformin, or both, AQP2 phosphorylation at S261 was decreased with PDBu or metformin alone, but there was no additive effect on phosphorylation with PDBu and metformin together...AMPK activation promotes water reabsorption, but the mechanism remains to be determined. PKC and AMPK do not appear to act synergistically to regulate water reabsorption.
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