AmpK AND lactic acid

The objective of this study was to determine the effects of shackling and wing flapping on stress, postmortem metabolism, AMP-activated protein kinase (AMPK), and quality of broiler pectoralis major. Before slaughter, a total of 80 Arbor Acres broilers was randomly categorized into 2 replicate pens (40 broilers per pen) and each pen randomly divided into 2 groups (shackling, T; control, C). Corticosterone, creatine kinase, and lactate dehydrogenase were determined on blood plasma parameters. Pectoralis major were removed after evisceration and used for determination of energy metabolism, meat quality, and AMPK phosphorylation...

Loss-of-function of succinate dehydrogenase-B (SDHB) is a predisposing factor of aerobic glycolysis and cancer progression. Adenosine monophosphate activated protein kinase (AMPK) is involved in the regulation of aerobic glycolysis and the diverse hallmarks of cancer. The present study investigated whether AMPK mediated the regulatory effects of SDHB in aerobic glycolysis and cancer growth. The expression of SDHB and AMPK in colorectal cancer (CRC) and normal tissues was assessed by western blotting. HT-29 CRC cells were used to establish in vitro models of ectopic overexpression and knockdown of SDHB...

Human proteins MTO1 and GTPBP3 are thought to jointly catalyze the modification of the wobble uridine in mitochondrial tRNAs. Defects in each protein cause infantile hypertrophic cardiomyopathy with lactic acidosis. However, the underlying mechanisms are mostly unknown. Using fibroblasts from an MTO1 patient and MTO1 silenced cells, we found that the MTO1 deficiency is associated with a metabolic reprogramming mediated by inactivation of AMPK, down regulation of the uncoupling protein 2 (UCP2) and transcription factor PPARγ, and activation of the hypoxia inducible factor 1 (HIF-1)...

Metformin, currently recommended as the drug of first choice in type 2 diabetes mellitus (T2DM), is one of the few antihiperglycemic drugs to reduce cardiovascular risk. Nonetheless, due to the risk of lactic acidosis during metformin therapy, its usage in patients with diabetes and heart failure (HF) is still a matter of debate. The aim of this review is to present data supporting the possibility of using metformin in the treatment of diabetic patients with concomitant heart failure. In the failing heart, metformin through the mechanism related to AMP-activated protein kinase (AMPK) activity, improves free fatty acids (FFA) and glucose metabolism, mitochondrial biogenesis, as well as nitric oxide (NO)-NO synthase pathway...

MicroRNAs play an important role in tumor development and progression. Tumor growth is closely associated with glucose metabolism. Specifically, tumor cells produce energy (ATP) under aerobic and anaerobic conditions through glycolysis and metabolites, such as lactic acid and ATP, as a result of the Warburg effect. However, the transport of glucose into cells depends on protein transporters in the cell membrane. Therefore, this area has recently become a topic of interest for research on targeted cancer therapy...

Adenosine monophosphate-activated protein kinase (AMPK) is a prevalent mammalian energy metabolism sensor, but little is known about its role as an energy sensor in fish experiencing stress. We aimed to study AMPK in Oreochromis niloticus on both the molecular and the physical level. We found that the cDNAs encoding the AMPKα1 and AMPKα2 variants of the O. niloticus catalytic α subunit were 1753bp and 2563 bp long and encoded 571 and 557 amino acids, respectively. Both the AMPKα1 and the AMPKα2 isoform possess structural features similar to mammalian AMPKα, including a phosphorylation site at Thr172 in the N-terminus, and exhibit high homology with other fish and vertebrate AMPKα sequences (81...

BACKGROUND AND OBJECTIVE: Metformin hydrochloride (MTF-HCl) is extensively recommended by physicians for the treatment of polycystic ovary syndrome (PCOS). Mechanistically, MTF-HCl activates AMP-dependent kinase-α (AMPK-α) pathway to decrease the glucose production, enhances fatty acid oxidation and elevates the uptake of glucose in tissues. However, despite favourable physicochemical properties, oral administration of MTF-HCl is associated with impaired bioavailability (50-60%), lactic-acidosis and frequent dosing (500mg 2-3 times a day) in PCOS that ultimately influence the patient compliance...

Metabolism of bladder cancer represents a key issue for cancer research. Several metabolic altered pathways are involved in bladder tumorigenesis, representing therefore interesting targets for therapy. Tumor cells, including urothelial cancer cells, rely on a peculiar shift to aerobic glycolysis-dependent metabolism (the Warburg-effect) as the main energy source to sustain their uncontrolled growth and proliferation. Therefore, the high glycolytic flux depends on the overexpression of glycolysis-related genes (SRC-3, glucose transporter type 1 [GLUT1], GLUT3, lactic dehydrogenase A [LDHA], LDHB, hexokinase 1 [HK1], HK2, pyruvate kinase type M [PKM], and hypoxia-inducible factor 1-alpha [HIF-1α]), resulting in an overproduction of pyruvate, alanine and lactate...

AMP activated protein kinase (AMPK) is a pivotal metabolic regulatory enzyme and novel target of controlling inflammation. Our previous studies had demonstrated that 5-amino-4-imidazolecarboxamide riboside (AICAR), an AMPK activator, attenuated lipopolysaccharide (LPS)/D-galactosamine (D-gal)-induced fulminant hepatitis via suppressing inflammatory response. Since inflammation usually activates the coagulation response and aggravates inflammation-induced tissue injury, the present study was to explore the effects of AICAR on inflammation-induced activation of coagulation...

Anticancer potential of metformin has been extensively studied. However, its anticancer clinical use remains yet to be approved since sufficient concentration on target organs could not be achieved via conventional administration. To overcome this drawback, we aim to examine the efficiency of novel intravesical treatment of metformin on syngeneic orthotopic preclinical model. Three human and one murine bladder cancer cell lines were tested in vitro for inhibitory sensitivity by MTT and cologenic assays. AMPK pathway including AKT, Erk and S6K was examined by western blot and further explored by regulating activated levels using specific inhibitors...

GTPBP3 is an evolutionary conserved protein presumably involved in mitochondrial tRNA (mt-tRNA) modification. In humans, GTPBP3 mutations cause hypertrophic cardiomyopathy with lactic acidosis, and have been associated with a defect in mitochondrial translation, yet the pathomechanism remains unclear. Here we use a GTPBP3 stable-silencing model (shGTPBP3 cells) for a further characterization of the phenotype conferred by the GTPBP3 defect. We experimentally show for the first time that GTPBP3 depletion is associated with an mt-tRNA hypomodification status, as mt-tRNAs from shGTPBP3 cells were more sensitive to digestion by angiogenin than tRNAs from control cells...

The mechanism whereby lactic acid bacteria extend the lifespan of Caenorhabditis elegans has previously been elucidated. However, the role of Weissella species has yet not been studied. We show that Weissella koreensis and Weissella cibaria significantly (p < 0.05) extend the lifespan of C. elegans compared with Escherichia coli OP50 and induce the expression of several genes related to lifespan extension (daf-16, aak-2, jnk-1, sod-3 and hif-1). Oral administration of Weissella altered reactive oxygen species (ROS) production and lowered the accumulation of lipofuscin and increased locomotor activity (which translates to a delay in ageing)...

Enhancement of muscular energy production is thought to improve locomotive functions and prevent metabolic syndromes including diabetes and lipidemia. Black ginger (Kaempferia parviflora) has been cultivated for traditional medicine in Thailand. Recent studies have shown that black ginger extract (KPE) activated brown adipocytes and lipolysis in white adipose tissue, which may cure obesity-related dysfunction of lipid metabolism. However, the effect of KPE on glucose and lipid utilization in muscle cells has not been examined yet...

Cordyceps militaris has been used extensively as a crude drug and a folk tonic food in East Asia due to its various pharmacological activities. Our study aims to investigate the effect of Cordyceps militaris fruit body extract (CM) on antifatigue in mouse model. Two week CM administration significantly delayed fatigue phenomenon which is confirmed via rotating rod test, forced swimming test and forced running test. Compared to nontreated mouse, CM administration increased ATP levels and antioxidative enzymes activity and reduced the levels of lactic acid, lactic dehydrogenase, malondialdehyde, and reactive oxygen species...

The aim of this study was to determine the effects of pre-slaughter transport during summer and subsequent water shower spray on stress, postmortem glycolysis, energy metabolism and adenosine monophosphate-activated protein kinase (AMPK) in Pectoralis major (PM) muscle of broilers. Results indicated that transport during high ambient temperature induced the release of plasma corticosterone, which significantly affected stress conditions. Moreover, we found a lower energy status in the early postmortem period compared to the control group...

Lactic acid generated by highly glycolytic tumours is exported by the MonoCarboxylate Transporters, MCT1 and MCT4, to maintain pHi and energy homeostasis. We report that MCT1 inhibition combined with Mct4 gene disruption severely reduced glycolysis and tumour growth without affecting ATP levels. Because of the key role of the 5'-AMP-activated protein kinase (AMPK) in energy homeostasis, we hypothesized that targeting glycolysis (MCT-blockade) in AMPK-null (Ampk(-/-)) cells should kill tumour cells from 'ATP crisis'...

Metformin, a biguanide, is considered in EASD and ADA to be a first-line glucose-lowering agent for patients with type 2 diabetes. The effectiveness of metformin as an anti-diabetic drug is explained by its ability to lower blood glucose by decreasing hepatic glucose production, stimulating glucose uptake in the muscle, and increasing fatty acid oxidation in adipose tissue. The exact mechanism of this effect has not been fully understood, but metformin is thought to activate hepatic AMP-activated protein kinase (AMPK), and it suppresses liver glucagon signal by increasing AMP due to inhibition of mitochondrial respiratory complex I...

Dihydromyricetin (DMY), the major bioactive flavonoid ingredient extracted from the leaves of Ampelopsis grossedentata (Hand.-Mazz) W.T. Wang, displays multiple pharmacological activities, including oxidation resistance, antitumor properties and free radical scavenging capacities. However, the role of DMY in methylglyoxal (MG)-induced diabetes-associated cognitive decline and its underlying molecular mechanisms are unclear. The aim of the present study was to evaluate the effects of DMY on oxidative stress and glucose transport activity in a MG-induced PC12 cell line and to explore the related mechanisms...

DMH1(4-[6-(4-Isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl] quinoline) is a compound C analogue with the structural modifications at the 3- and 6-positions in pyrazolo[1,5-a]pyrimidine backbone. Compound C was reported to inhibit both AMPK and Akt. Our preliminary work found that DMH1 activated Akt. Since Akt was involved in glucose metabolism, we aimed to identify the effects of DMH1 on glucose metabolism in L6 rat muscle cells and the potential mechanism. Results showed that DMH1 increased lactic acid release and glucose consumption in L6 rat muscle cells in a dose-dependent manner...

SNF1/AMPK protein kinase plays important roles in fungal development and activation of catabolite-repressed genes. In this study, we characterized the role of the Beauveria bassiana SNF1 ortholog. The vegetative growth of the ΔBbSNF1 mutant was reduced by 16 to 50 % on diverse carbon/nitrogen sources. Transcriptional analysis revealed a collection of proteases and chitinases that were not induced when the mutant was grown on complex carbon/nitrogen sources. BbSNF1 also contributes to extracellular acidification...