A5031413129- Metabolism, Diabetes, and Cancer
- Cellular transport and secretion
- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Calcium signaling and nucleotide metabolism
- Peroxisome Proliferator-Activated Receptors
- Muscle Physiology and Disorders
- Retinal Development and Disorders
- Photosynthetic Processes and Mechanisms
- Skin and Cellular Biology Research
- Biochemical and Structural Characterization
- Photoreceptor and optogenetics research
- Lipid Membrane Structure and Behavior
- Glycogen Storage Diseases and Myoclonus
- Cancer-related Molecular Pathways
- Lysosomal Storage Disorders Research
- Diet and metabolism studies
- Genetic Neurodegenerative Diseases
- Receptor Mechanisms and Signaling
- Biotin and Related Studies
- Genetics and Neurodevelopmental Disorders
- Exercise and Physiological Responses
- Protein Kinase Regulation and GTPase Signaling
- Muscle metabolism and nutrition
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
University of Dundee
2000-2024
University of Aberdeen
2007
University of California, San Francisco
2001-2005
San Francisco Foundation
2001-2005
Stanford University
2005
The AMP-activated protein kinase (AMPK) system acts as a sensor of cellular energy status that is conserved in all eukaryotic cells. It activated by increases the AMP:ATP ratio caused metabolic stresses either interfere with ATP production (eg, deprivation for glucose or oxygen) accelerate consumption muscle contraction). Activation response to AMP involves phosphorylation an upstream kinase, tumor suppressor LKB1. In certain cells neurones, endothelial cells, and lymphocytes), AMPK can also...
A wide variety of agents activate AMPK, but in many cases the mechanisms remain unclear. We generated isogenic cell lines stably expressing AMPK complexes containing AMP-sensitive (wild-type, WT) or AMP-insensitive (R531G) γ2 variants. Mitochondrial poisons such as oligomycin and dinitrophenol only activated WT cells, did AICAR, 2-deoxyglucose, hydrogen peroxide, metformin, phenformin, galegine, troglitazone, phenobarbital, resveratrol, berberine. Excluding all these also inhibited cellular...
Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), and adiponectin increases glucose uptake. The aim this study was to determine whether AICAR stimulates uptake humans. We studied 29 healthy men (aged 26 +/- 8 years, BMI 25 4 kg/m(2) [mean SD]). Rates 2-deoxyglucose (2DG) were determined measuring accumulation total 2DG (2DG 2DG-6-phosphate) during a primed, continuous infusion. effects...
LKB1 was discovered as a tumour suppressor mutated in Peutz-Jeghers syndrome, and is gene involved cell polarity well an upstream protein kinase for members of the AMP-activated family. We report that mammals express two splice variants caused by alternate usage 3′-exons. LKB1L previously described form, while LKB1S novel form which last 63 residues are replaced unique 39-residue sequence lacking known phosphorylation (Ser431) farnesylation (Cys433) sites. Both isoforms widely expressed...
Lafora progressive myoclonus epilepsy is a fatal neurodegenerative disorder caused by defects in the function of at least two proteins: laforin, dual-specificity protein phosphatase, and malin, an E3-ubiquitin ligase. In this study, we report that functional laforin-malin complex promotes ubiquitination AMP-activated kinase (AMPK), serine/threonine acts as sensor cellular energy status. This reaction occurs when any three AMPK subunits (alpha, beta, gamma) are expressed individually cell, it...
The goal of the current work was to profile positive (mTORC1 activation, autocrine/paracrine growth factors) and negative [AMPK, unfolded protein response (UPR)] pathways that might regulate overload-induced mTORC1 (mTOR complex 1) activation with hypothesis a number regulators will be engaged during supraphysiological model hypertrophy. To achieve this, mTORC1-IRS-1/2 signaling, BiP/CHOP/IRE1α, AMPK were determined in rat plantaris muscle following synergist ablation (SA). SA resulted...
In humans, there are two isoforms each of clathrin heavy chain (CHC17 and CHC22) light (LCa LCb) subunits, all encoded by separate genes. CHC17 forms the ubiquitous clathrin-coated vesicles that mediate membrane traffic. CHC22 is implicated in specialized organization skeletal muscle. bound regulated LCa LCb, whereas does not functionally interact with either chain. The imbalanced interactions between subunit suggest a distinct evolutionary history for isoform pair. Phylogenetic sequence...
Performing exercise in a glycogen depleted state increases skeletal muscle lipid utilization and the transcription of genes regulating mitochondrial β-oxidation. Potential candidates for glycogen-mediated metabolic adaptation are peroxisome proliferator activated receptor (PPAR) coactivator-1α (PGC-1α) factor/nuclear PPAR-∂. It was therefore aim present study to examine whether acute with or without manipulation affects PGC-1α PPAR-∂ function rodent muscle. Twenty female Wistar rats were...
Skeletal muscle triglyceride accumulation is associated with insulin resistance in obesity. Recently, it has been suggested that α lipoic acid (ALA) improves sensitivity by lowering nonadipose tissues via activation of skeletal AMP-activated protein kinase (AMPK). We examined whether chronic ALA supplementation prevents muscular lipid high-fat diets AMPK. In addition, we tested if was able to improve rats fed low- and (LFD, HFD). Supplementing male Wistar 0.5% for 8 weeks significantly...
The muscle isoform of clathrin heavy chain, CHC22, has 85% sequence identity to the ubiquitously expressed CHC17, yet its expression pattern and function appear be distinct from those well-characterized clathrin-coated vesicles. In mature CHC22 is preferentially concentrated at neuromuscular myotendinous junctions, suggesting a role sarcolemmal contacts with extracellular matrix. During myoblast differentiation, increased, initially localized desmin nestin then segregated poles fused...
Clathrin-coated vesicles execute receptor-mediated endocytosis at the plasma membrane. However, a role for clathrin in later endocytic trafficking processes, such as receptor sorting and recycling or maintaining organization of pathway, has not been thoroughly characterized. The existence clathrin-coated buds on endosomes suggests that might mediate events. To investigate function endosomal membranes, endosome distribution were analyzed HeLa cell line expresses dominant-negative inhibitor...
Mammalian AMP-activated protein kinase is a serine/threonine that acts as sensor of cellular energy status. heterotrimer three different subunits, i.e. alpha, beta, and gamma, with alpha being the catalytic subunit beta gamma having regulatory roles. Although several studies have defined domains in involved interaction other subunits complex, little known about regions these interactions. To study this, we made sequential deletions from N termini isoforms studied interactions both by...
We demonstrated previously that, in healthy young men, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR) stimulates human muscle 2-deoxyglucose (2DG) uptake without detectable activation of AMP-activated protein kinase (AMPK) but with extracellular-regulated 1/2 (ERK1/2) activation. tested whether AICAR 2DG older patients or type 2 diabetes (T2D). Six subjects (23 +/- 3 yr, BMI 25 kg/m(-2); means SE), eight (59 4 28 kg/m(-2)), and T2D (62 27 kg/m(-2)) received a 6-h infusion...
AMPK is an energy sensor that regulates cellular functions in response to changes availability. However, whether activity spatially regulated, and the implications for cell function, have been unclear. We now report associates with Golgi apparatus, its activation by two specific pharmacological activators leads fragmentation similar caused antibiotic Golgicide A, inhibitor of Golgi-specific Brefeldin A resistance Factor-1 (GBF1), a guanine nucleotide exchange factor targets ADP-Ribosylation...
Performing exercise with low muscle glycogen has profound effects on substrate utilization and gene transcription. The aim of the present study was to examine signaling pathways potentially responsible for modulating transcription during in a glycogen-depleted state. Methods Twenty female Wistar rats were randomly assigned 5 experimental groups: control [CON]; normal [NG-C]; [NG-E]; [LG-C]; [LG-E]). Results Exercise reduced by 47 75% post NG-E LG-E groups respectively. protocol meant that...