- |||||||||| Preclinical, Journal: Zingerone ameliorates non-alcoholic fatty liver disease in rats by activating AMPK. (Pubmed Central) - Jul 10, 2022
PRACTICAL APPLICATIONS: The findings of this study identified Zingerone, isolated from ginger, as a very effective drug that not only can attenuate fasting hyperglycemia and hyperlipidemia, but also prevent hepatic deposition, steatosis, and oxidative damage induced by high-fat-fed rats by activating the AMPK/Nrf2 antioxidant axis and concomitant suppression of SREBP1, SREBp2, and NF-κB p65. These data list Zingerone as a potent stimulator of AMPK which suggests an effective strategy to treat and alleviate NAFLD and encourages further translational and clinical trials.
- |||||||||| metformin / Generic mfg.
Journal, PARP Biomarker: Metformin Induces PRODH/POX-Dependent Apoptosis in Breast Cancer Cells. (Pubmed Central) - Jun 24, 2022
The mechanism for MET-induced apoptosis involves the up-regulation of prolidase activity and a decrease in collagen biosynthesis contributing to an increase in the concentration of substrate (proline) for PRODH/POX-dependent ROS formation and activation of caspases -9 and -8. The data suggest that PRODH/POX participates in the MET-induced intrinsic and extrinsic apoptosis in MCF-7 cells.
- |||||||||| rosiglitazone / Generic mfg.
Preclinical, Journal: HM-Chromanone Ameliorates Hyperglycemia and Dyslipidemia in Type 2 Diabetic Mice. (Pubmed Central) - May 21, 2022
Mice were separated into three groups: db/db, rosiglitazone and HMC...Consequently, HMC reduced hyperglycemia by improving the expression of insulin-resistance-related genes and improved dyslipidemia by regulating fatty acid synthase and oxidation-related genes in db/db mice. Therefore, HMC could ameliorate hyperglycemia and dyslipidemia in type 2 diabetic mice.
- |||||||||| Androgen excess inhibits decidualization in human endometrial stromal cells via AMPK/SIRT1/PDK4 pathway (Grand Hall C) - May 6, 2022 - Abstract #ASRI2022ASRI_33;
We highly suspect that pregnancy failure of PCOS with hyperandrogenism may be due to reduced PDK4- mediated glucose metabolism, resulting in disrupted decidualization. This study proposes a possible mechanism to explain how hyperandrogenism affects endometrial decidualization and provides valuable information for understanding the underlying mechanism of interaction between endocrine and metabolism during Decidualization.
- |||||||||| Preclinical, Journal: Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice. (Pubmed Central) - Apr 5, 2022
Furthermore, the ability of AdipoRon to stimulate AMPK and PGC1a was conserved in nonhuman primate cultured cells. These data show that AdipoRon is an effective agent for the prevention of sarcopenia in mice and indicate that its effects translate to primates, suggesting it may also be a suitable therapeutic for sarcopenia in clinical application.
- |||||||||| Preclinical, Journal: DRD1 agonist A-68930 improves mitochondrial dysfunction and cognitive deficits in a streptozotocin-induced mouse model. (Pubmed Central) - Mar 23, 2022
Moreover, our mechanism researches revealed that the DRD1 signaling induced by A-68930 significantly rescued STZ-induced mitochondrial biogenesis deficit, mitochondrial dysfunction, Aβ overexpression, and tau phosphorylation in mice hippocampus and cortex and SH-SY5Y cells, which may be mediated through stimulating AMPK/PGC-1α pathway. This study indicates that DRD1 agonist A-68930 can improve STZ-induced cognitive deficits and mitochondrial dysfunction in vivo and in vitro, and DRD1 may represent an appropriate target candidate for AD drug development.
- |||||||||| Niagen (nicotinamide riboside) / ChromaDex
Review, Journal: Nutraceutical and Dietary Strategies for Up-Regulating Macroautophagy. (Pubmed Central) - Mar 11, 2022
SIRT1 activation may be achieved with a range of agents, including ferulic acid, melatonin, urolithin A, N1-methylnicotinamide, nicotinamide riboside, and glucosamine; correction of ubiquinone deficiency may also be useful in this regard, as may dietary strategies such as time-restricted feeding or intermittent fasting...Low-protein plant-based diets could be expected to increase ATF4 and CHOP expression, while diminishing IGF-I-mediated activation of AKT and mTORC1. Hence, practical strategies for protecting health by up-regulating macroautophagy may be feasible.
- |||||||||| Journal: The Imbalance of Mitochondrial Fusion/Fission Drives High-Glucose-Induced Vascular Injury. (Pubmed Central) - Jan 19, 2022
As the guardian of mitochondria, AMPK is suppressed in response to hyperglycemia, resulting in imbalanced mitochondrial fusion/fission, which can be reversed by AMPK stimulation. Our results suggest that mitochondrial fusion/fission's staged homeostasis may be a predictive factor of diabetic cardiovascular complications.
- |||||||||| metformin / Generic mfg.
Journal, IO biomarker: Stimulation of AMPK Prevents Diabetes-Induced Photoreceptor Cell Degeneration. (Pubmed Central) - Dec 30, 2021
In vitro, 661w cells were treated with AGEs with/without an AMPK agonist (metformin) or AMPK inhibitor (compound C)...However, AMPK stimulation ameliorated this effect. These results indicate that AMPK stimulation can delay diabetes-induced photoreceptor degeneration by regulating autophagy and mitochondrial function.
- |||||||||| metformin / Generic mfg.
Journal: Rapamycin-induced hyperglycemia is associated with exacerbated age-related osteoarthritis. (Pubmed Central) - Oct 30, 2021
This is the first study to show that Rap induced increase in plasma glucose was associated with greater OA severity. Further, articular cartilage mTORC1 inhibition and bodyweight reduction by dietary Rap and Rap+Met did not appear to protect against primary OA during the prevailing hyperglycemia.
- |||||||||| Review, Journal: The role of AMPK in regulation of Na,K-ATPase in skeletal muscle: does the gauge always plug the sink? (Pubmed Central) - Oct 28, 2021
However, different models suggest that AMPK does not inhibit or even stimulates NKA in skeletal muscle, which appears to contradict the idea that AMPK maintains the cellular energy balance by always suppressing ATP-consuming processes. In this short review, we examine the role of AMPK in regulation of NKA in skeletal muscle and discuss the apparent paradox of AMPK-stimulated ATP consumption.
- |||||||||| Preclinical, Journal: Mitochondrial dysfunction in skeletal muscle of fukutin deficient mice is resistant to exercise- and AICAR-induced rescue. (Pubmed Central) - Oct 22, 2021
The beneficial effects of AMPK stimulation via AICAR on muscle contractile function may be partially explained by AMPK's other role of regulating skeletal muscle autophagy, a cellular process critical for clearance of damaged and/or dysfunctional organelles. Two primary conclusions can be drawn from this data, 1) fukutin deletion produces intrinsic muscular metabolic defects that likely contribute to dystroglycanopathy disease pathology, and 2) AICAR treatment accelerates recovery of muscle contractile function following injury suggesting AMPK signaling as a possible target for therapeutic strategies.
- |||||||||| progesterone / Generic mfg.
Journal: PKA and AMPK Signaling Pathways Differentially Regulate Luteal Steroidogenesis. (Pubmed Central) - Oct 22, 2021
The small and large luteal cells produce progesterone, a steroid hormone required for establishment and maintenance of pregnancy...Additionally, LH/PKA increased phosphorylation of HSL at Ser563, which is crucial for enzyme activation, and decreased inhibitory phosphorylation of HSL at Ser565. The findings indicate that LH and AMPK exert opposite post-translational modifications of HSL, presumptively regulating cholesterol availability for steroidogenesis.
- |||||||||| Nexletol (bempedoic acid) / Esperion Therap, Otsuka
[VIRTUAL] Beneficial Effects of Bempedoic Acid Treatment in ADPKD Mice () - Oct 17, 2021 - Abstract #KIDNEYWEEK2021KIDNEY_WEEK_1862;
BA significantly reduced kidney injury markers and mTOR and ERK signaling. BA may be a promising new ADPKD therapy, having beneficial effects on disease severity when used alone and with tolvaptan in mice.
- |||||||||| MG132 / Jilin University, Dorothy M. Davis Heart and Lung Research Institute
Preclinical, Journal: Role of AMP-activated protein kinase during postovulatory aging of mouse oocytes†. (Pubmed Central) - Oct 13, 2021
This study showed that AMPK activation with metformin or 5-aminoimidazole- 4-carboxamide- 1-beta-d- ribofuranoside and inactivation with compound C significantly increased and decreased, respectively, the activation susceptibility (AS) and other aging parameters in aging mouse oocytes...MPF upregulation with MG132 or downregulation with roscovitine completely abolished the effects of AMPK activation or inactivation on AS of aging oocytes, respectively...Furthermore, treatment with Ca2+/calmodulin-dependent protein kinase (CaMK) inhibitors significantly decreased AS and AMPK activation. Taken together, the results suggested that AMPK facilitated oocyte aging through inhibiting MPF activities, and postovulatory oocyte aging activated AMPK with decreased cAMP by activating CaMKs via increasing ROS and cytoplasmic calcium.
- |||||||||| metformin / Generic mfg.
Journal: IQGAP1 binds AMPK and is required for maximum AMPK activation. (Pubmed Central) - Sep 16, 2021
The ability of metformin and increased intracellular free Ca concentrations to activate AMPK is reduced in cells lacking IQGAP1...Comparison of the fasting response in wild-type and IQGAP1-null mice revealed that transcriptional regulation of the gluconeogenesis genes PCK1 and G6PC and the fatty acid synthesis genes FASN and ACC1 is impaired in IQGAP1-null mice. Our data disclose a previously unidentified functional interaction between IQGAP1 and AMPK and suggest that IQGAP1 modulates AMPK signaling.
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
Journal: The novel interplay between CD44 standard isoform and the caspase-1/IL1B pathway to induce hepatocellular carcinoma progression. (Pubmed Central) - Sep 9, 2021
Accumulating data indicate caspase-1 (CASP1), one of the inflammatory caspases, promotes hepatocellular carcinoma (HCC) progression in tumor proliferation, invasion, EMT phenotype and sorafenib resistance...Lastly, hypoxia-mediated caspase-1/IL1B overexpression could be abolished by CD44s downregulation through decreasing HIF1A and enhancing autophagic activity. Overall, targeting CD44s is a novel inhibitory mechanism of caspase-1/IL1B expression, both in normoxia and hypoxia conditions.
- |||||||||| metformin / Generic mfg.
Preclinical, Journal: Pre-extinction activation of hippocampal AMPK prevents fear renewal in mice. (Pubmed Central) - Sep 3, 2021
Furthermore, we also found that metformin, a first-line antidiabetic drug, was capable of preventing fear renewal in male mice by stimulating AMPK in dorsal hippocampus. Collectively, our study provides insight into the role of hippocampal AMPK in regulation of fear renewal and indicates that increasing activity of hippocampal AMPK can prevent fear renewal, thus enhancing the potency of exposure therapy.
- |||||||||| Journal: An Organelle-Specific Nanozyme for Diabetes Care in Genetically or Diet-Induced Models. (Pubmed Central) - Aug 4, 2021
More importantly, intraperitoneal administration of Fe O NPs stimulates AMPK activities in metabolic tissues, reduces blood glucose levels, and improves glucose tolerance and insulin sensitivity in diabetic ob/ob mice. The study reveals intrinsic organelle-specific properties of Fe O NPs in AMPK activation, glycemic control, and insulin-resistance improvement, suggesting their potential efficacy in diabetes care.
- |||||||||| Journal: GPR120 facilitates cholesterol efflux in macrophages through activation of AMPK signaling pathway. (Pubmed Central) - May 25, 2021
Because only free cholesterol can be effluxed from macrophages, we found that activation of AMPK could lead to increase both neutral cholesteryl esters hydrolysis by upregulation of neutral cholesterol ester hydrolase (NCEH) expression and acid cholesteryl esters hydrolysis by activation of ULK1. In conclusion, these results demonstrated that GPR120 facilitated ABCA1- and ABCG1-mediated cholesterol efflux through activation of PLC/Ca /CaMKK/AMPK signaling pathway, which induced cholesteryl ester hydrolysis and elevated the expression of ABCA1 and ABCG1 in macrophages.
- |||||||||| Preclinical, Journal: Adiponectin stimulates glucose uptake in mouse blastocysts and embryonic carcinoma cells. (Pubmed Central) - May 8, 2021
In mouse embryos adiponectin acts as a hormonal regulator of glucose uptake, which becomes especially important in phases with reduced levels of circulating insulin. Our results suggest that adiponectin maintains the glucose supply for early embryos under hypoinsulinaemic conditions, for example, in mothers suffering from type 1 diabetes mellitus.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Preclinical, Journal: Effects of treadmill exercise on the regulation of tight junction proteins in aged mice. (Pubmed Central) - Apr 28, 2021
In in vitro study, doxorubicin that induces cell senescence was treated to Caco2 cells (colon cell) to mimic aging effect...Zonulin, which is known as degrading tight junction protein, is not significantly changed by both age and exercise. This study compared that tight junction protein expression level in old mice compared to its level in young mice, and also clarified that the effect of treadmill exercise on tight junction protein in both young and old mice.
|
