- |||||||||| Journal: AMPK stimulation inhibits YAP/TAZ signaling to ameliorate hepatic fibrosis. (Pubmed Central) - Mar 7, 2024
In the carbon tetrachloride mouse model of fibrosis, pharmacologic activation of AMPK in HSCs inhibits YAP/TAZ signaling and reduces fibrosis. The findings implicate AMPK as a critical regulator of YAP/TAZ signaling and HSC inactivation and highlight AMPK activation as a therapeutic target for the treatment of hepatic fibrosis.
- |||||||||| atorvastatin / Generic mfg.
Review, Journal: A Dual Pharmacological Strategy against COVID-19: The Therapeutic Potential of Metformin and Atorvastatin. (Pubmed Central) - Feb 24, 2024 Nevertheless, the journey from observing something to applying it in a therapeutic setting is intricate, and the inherent diversity of the data necessitates carefully executed, forward-looking clinical trials. This review highlights the requirement for efficacious, easily obtainable, and secure COVID-19 therapeutics and identifies MET and ATO as promising treatments in this worldwide health emergency.
- |||||||||| Journal: Regulated dynamic subcellular GLUT4 localization revealed by proximal proteome mapping in human muscle cells. (Pubmed Central) - Dec 21, 2023
AMPK-stimulated translocation involves GLUT4 redistribution among the same compartments traversed in unstimulated cells, with a significant recruitment of GLUT4 from the Golgi and trans-Golgi network compartments. Our comprehensive proximal protein mapping provides an integrated, high-density, whole-cell accounting of the localization of GLUT4 at a resolution of ?20?nm that serves as a structural framework for understanding the molecular mechanisms regulating GLUT4 trafficking downstream of different signaling inputs in a physiologically relevant cell type.
- |||||||||| P39 as an ZMP Prodrug Activator of AMPK Enhances Accumbal Dopamine Function (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_11278;
The present studies reinforce ZMP as a key modulator of AMPK-activated dopamine release which has implications for delayed cognitive deficits observed in aging. The present studies were performed using methods to ensure scientific rigor, including experimenter blinding when possible, statistical analysis and appropriate sample sizing for replication and hypothesis testing.
- |||||||||| torkinib (PP242) / Takeda, UCSF Medical Center
Journal: Prior Treatment with AICAR Causes the Selective Phosphorylation of mTOR Substrates in C2C12 Cells. (Pubmed Central) - Oct 27, 2023 The exposure of cells to rapamycin (an mTORC1 inhibitor) and PP242 (an inhibitor of both mTOR complexes) revealed the differential phosphorylation of mTORC2 substrates. Taken together, the data suggest that prior exposure to AICAR causes the selective phosphorylation of mTOR substrates, even after prolonged recovery in a nutrient-replete medium.
- |||||||||| Preclinical, Journal: A Combination of Soy Isoflavone and L-Carnitine Improves Running Endurance in Mice. (Pubmed Central) - Sep 13, 2023
Collectively, these findings suggest that APIC supplementation enhances mitochondrial biogenesis, promotes a switch from glycolytic to oxidative fiber types, and improves fatty acid metabolism through the activation of the AMPK signaling pathway in murine skeletal muscle. Ultimately, these effects contribute to the enhancement of running endurance.
- |||||||||| metformin / Generic mfg.
Review, Journal: Metabolic Complications of Glucocorticoids - Prevention by Metformin. (Pubmed Central) - Jul 17, 2023 Moreover, patients had a lower risk of developing pneumonia and a reduced number of admissions to hospital, representing financial advantage for the health service. We believe that the routine use of metformin for patients on glucocorticoid treatment would represent a key advantage in the care for this patient population.
- |||||||||| Mifeprex (mifepristone) / Danco Laboratories
Membrane Progesterone Receptors Induce Glycogenolysis in Uterine Epithelial Cells (ENDOExpo) - May 11, 2023 - Abstract #ENDO2023ENDO_1502; RU486 did not block progesterone's effect, indicating that the effect of progesterone was not mediated by nuclear progesterone receptors (nPR)...In a human model, progesterone and Org OD 02-0 decreased glycogen levels to a similar extent in Ishikawa cells that express mPRs but not nPRs (P=0.0027). In conclusion, progesterone acting through the mPR and AMPK to stimulate glycogenolysis may play a crucial role in providing glucose to endometrial tissue or the growing embryo.
- |||||||||| Preclinical, Journal: VCE-005.1, an hypoxia mimetic betulinic acid derivative, induces angiogenesis and shows efficacy in a murine model of traumatic brain injury. (Pubmed Central) - May 3, 2023
Furthermore, in CCI model, VCE-005.1 greatly improved locomotor coordination, increased neovascularization and preserved BBB integrity that paralleled with a large reduction of peripheral immune cells infiltration, recovering AMPK expression and reducing apoptosis in neuronal cells. Taken together, our results demonstrate that VCE-005.1 is a multitarget compound that shows anti-inflammatory and neuroprotective effects mainly by preventing BBB disruption and has the potential to be further developed pharmacologically in TBI and maybe other neurological conditions that concur with neuroinflammation and BBB disruption.
- |||||||||| Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
Journal: Mapping the metabolic reprogramming induced by sodium-glucose cotransporter 2 inhibition. (Pubmed Central) - Apr 11, 2023 In vivo metabolic labeling with 13C-glucose in normoglycemic and diabetic mice treated with or without dapagliflozin, followed by metabolomics and metabolic flux analyses, showed that, in diabetes, glycolysis and glucose oxidation are impaired in the kidney, liver, and heart...mTORC1 activity was inhibited by SGLT2i along with stimulation of AMPK in both normoglycemic and diabetic animals, possibly explaining the protective effects against kidney, liver, and heart diseases. Collectively, our findings suggest that SGLT2i induces metabolic reprogramming orchestrated by AMPK-mTORC1 signaling with common and distinct effects in various tissues with implications for diabetes and aging.
- |||||||||| Journal: Exercise-induced specialized proresolving mediators stimulate AMPK phosphorylation to promote mitochondrial respiration in macrophages. (Pubmed Central) - Nov 19, 2022
The traditionally claimed antidiabetic effect of O. nepalensis has been proved to be effective in lowering the blood glucose level through in vitro, in vivo and in silico analysis which will pave a way for the development of antidiabetic phytopharmaceutical drugs which can be validated through further clinical studies. Collectively, these results suggest that exercise stimulates proresolving lipid mediator biosynthesis and mitochondrial metabolism in macrophages via AMPK, which might contribute to the anti-inflammatory and CVD risk reducing effect of exercise.
- |||||||||| Preclinical, Journal: Krill Oil Inhibits Cholesterol Synthesis and Stimulated Cholesterol Excretion in Hypercholesterolemic Rats. (Pubmed Central) - Nov 2, 2022
Furthermore, it decreased the levels of P-selectin, sVCAM-1, and NO, as well as aortic wall thickness, demonstrating its role in the prevention of atherosclerosis. Thus, we suggest that krill oil supplementation can reduce LDL-cholesterol levels in the blood during hypercholesterolemia by stimulating the uptake of LDL-cholesterol into tissue and cholesterol excretion, as well as inhibition of cholesterol synthesis.
- |||||||||| doxycycline / Generic mfg.
Metabolomics and Mechanistic Approaches to Identify Therapeutic Targets for Progressive Kidney Disease (Exhibit Hall, Orange County Convention Center, West Building) - Oct 13, 2022 - Abstract #KIDNEYWEEK2022KIDNEY_WEEK_2848; Methods (1) To elucidate a metabolic mechanism through which MDM2 absence reduces mitochondrial biogenesis and promotes kidney dysfunction, we developed transgenic 3-4 months mice with doxycycline-inducible deletion of MDM2 in renal tubule cells (MDM2cKO)...We are currently exploring mechanisms that connect MDM2 to Leu and Ala and testing AMPK activation role in improving kidney function, metabolic outcome, and survival of MDMcKO mice. The outcomes of this study will lead to improved treatment approaches for metabolic-related kidney diseases such as DKD.
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