- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Muscle Physiology and Disorders
- Ion Transport and Channel Regulation
- Muscle metabolism and nutrition
- Ion channel regulation and function
- Exercise and Physiological Responses
- Mitochondrial Function and Pathology
- Diet and metabolism studies
- Cellular Mechanics and Interactions
- Cardiovascular and exercise physiology
- Adipokines, Inflammation, and Metabolic Diseases
- Peroxisome Proliferator-Activated Receptors
- Regulation of Appetite and Obesity
- Protein Kinase Regulation and GTPase Signaling
- Genetics and Physical Performance
- Diabetes and associated disorders
- Diabetes Treatment and Management
- Glycogen Storage Diseases and Myoclonus
- Metabolomics and Mass Spectrometry Studies
- Cellular transport and secretion
- Genetics, Aging, and Longevity in Model Organisms
- Neurobiology and Insect Physiology Research
- Mass Spectrometry Techniques and Applications
National Research Tomsk State University
2018-2025
Karolinska Institutet
2015-2024
Milbank Memorial Fund
2014
Institute of Molecular Medicine
1998-2013
Laboratoire d’immunologie intégrative du cancer
2010-2011
Karolinska University Hospital
1997-2009
Inserm
2009
Université de Montpellier
2009
RMIT University
2001
MRC Clinical Trials Unit at UCL
2001
Skeletal muscle contraction increases intracellular ATP turnover, calcium flux, and mechanical stress, initiating signal transduction pathways that modulate peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha)-dependent transcriptional programmes. The purpose of this study was to determine if the intensity exercise regulates PGC-1alpha expression in human skeletal muscle, coincident with activation signalling cascades known regulate transcription. Eight sedentary...
Skeletal muscle from strength- and endurance-trained individuals represents diverse adaptive states. In this regard, AMPK-PGC-1alpha signaling mediates several adaptations to endurance training, while up-regulation of the Akt-TSC2-mTOR pathway may underlie increased protein synthesis after resistance exercise. We determined effect prior training history on responses in seven strength-trained six males who undertook 1 h cycling at 70% VO2peak or eight sets five maximal repetitions isokinetic...
Serum starvation is one of the most frequently performed procedures in molecular biology and there are literally thousands research papers reporting its use. In fact, this method has become so ingrained certain areas that reports often simply state cells were serum starved without providing any factual details as to how procedure was carried out. Even so, we quite obviously lack unequivocal terminology, standard protocols, perhaps surprisingly, a common conceptual basis when performing...
The identification of microRNAs (miRNAs) has established new mechanisms that control skeletal muscle adaptation to exercise. present study investigated the mRNA regulation components miRNA biogenesis pathway (Drosha, Dicer and Exportin-5), enriched miRNAs, (miR-1, -133a, -133b -206), several miRNAs dysregulated in myopathies (miR-9, -23, -29, -31 -181). Measurements were made biopsies from nine healthy untrained males at rest, 3 h following an acute bout moderate-intensity endurance cycling...
The aim of the study was to investigate effect resistance exercise alone or in combination with oral intake branched-chain amino acids (BCAA) on phosphorylation 70-kDa S6 protein kinase (p70(S6k)) and mitogen-activated (MAPK), extracellular signal-regulated (ERK1/2), p38 MAPK skeletal muscle. Seven male subjects performed one session quadriceps muscle training (4 x 10 repetitions at 80% repetition maximum) two occasions. In a randomized order, double-blind, crossover test, ingested solution...
AMP-activated protein kinase (AMPK) is a heterotrimeric that regulates glucose transport mediated by cellular stress or pharmacological agonists such as 5-aminoimidazole-4-carboxamide 1 β-d-ribonucleoside (AICAR). AS160, Rab GTPase-activating protein, provides mechanism linking AMPK signaling to uptake. We show AICAR increases AMPK, acetyl-CoA carboxylase, and AS160 phosphorylation insulin-independent mechanisms in isolated skeletal muscle. Recombinant complexes (α1β1γ1 α2β2γ1) phosphorylate...
The molecular signaling mechanisms by which muscle contractions lead to changes in glucose metabolism and gene expression remain largely undefined. We assessed whether exercise activates MAP kinase proteins (ERK1/2, SEK1, p38 kinase) as well Akt PYK2 skeletal from healthy volunteers obtained during after one-leg cycle ergometry at ∼70% VO2max. Exercise led a marked increase ERK1/2 phosphorylation, rapidly decreased resting levels upon recovery. increased phosphorylation of SEK1 lesser extent...
Level of physical activity is linked to improved glucose homeostasis. We determined whether exercise alters the expression and/or proteins involved in insulin-signal transduction skeletal muscle. Wistar rats swam 6 h per day for 1 or 5 days. Epitrochlearis muscles were excised 16 after last bout, and incubated with without insulin (120 nM). Insulin-stimulated transport increased 30% 50% days exercise, respectively. Glycogen content 2- 4-fold no change glycogen synthase expression. Protein...
AMP-activated protein kinase (AMPK) activation by AICAR (5-amino-imidazole carboxamide riboside) is correlated with increased glucose transport in rodent skeletal muscle via an insulin-independent pathway. We determined vitro effects of insulin and/or exposure on and cell-surface GLUT4 content from nondiabetic men type 2 diabetes. a dose-dependent manner healthy subjects. Insulin to similar extent control In contrast, insulin- AICAR-stimulated responses were impaired subjects Importantly,...
Fibroblast growth factor (FGF) 21, a novel member of the FGF family, plays role in variety endocrine functions, including regulation glucose and lipid metabolism. The FGF21 skeletal muscle is currently not known.Serum levels mRNA were determined normal tolerant (n = 40) type 2 diabetic (T2D; n subjects. We whether has direct effects on metabolism cultured myotubes 8) extensor digitorum longus muscle.Serum increased 20% T2D versus subjects (p < 0.05), whereas expression was unaltered. Fasting...
Dopamine inhibits Na+,K+-ATPase activity in renal tubule cells. This inhibition is associated with phosphorylation and internalization of the alpha subunit, both events being protein kinase C-dependent. Studies purified preparations, fusion proteins site-directed mutagenesis, heterologous expression systems have identified two major C residues (Ser-11 Ser-18) rat alpha1 subunit isoform. To identify site(s) that mediates endocytosis response to dopamine, we performed mutagenesis these...
Hypoglycemic sulfonylureas represent a group of clinically useful antidiabetic compounds that stimulate insulin secretion from pancreatic β cells. The molecular mechanisms involved are not fully understood but believed to involve inhibition potassium channels sensitive adenosine triphosphate (K ATP channels) in the cell membrane, causing membrane depolarization, calcium influx, and activation secretory machinery. In addition these effects, also promoted exocytosis by direct interaction with...
Rat L6, mouse C2C12, and primary human skeletal muscle cells (HSMCs) are commonly used to study biological processes in muscle, experimental data on these models abundant. However, consistently matched scarce, comparisons between the different cell types adult tissue problematic. We hypothesized that metabolic differences cellular may be reflected at mRNA level. Publicly available sets were profile levels myotubes tissues. HSMC assessed for proliferation, glucose uptake, glycogen synthesis,...
Curtailed sleep promotes weight gain and loss of lean mass in humans, although the underlying molecular mechanisms are poorly understood. We investigated genomic physiological impact acute peripheral tissues by obtaining adipose tissue skeletal muscle after one night full sleep. find that alters genome-wide DNA methylation tissue, unbiased transcriptome-, protein-, metabolite-level analyses also reveal highly tissue-specific changes partially reflected altered metabolite levels blood....
Signal transducer and activator of transcription 3 (STAT3) is involved in cytokine- nutrient-induced insulin resistance. The role STAT3 the development skeletal muscle resistance type 2 diabetes (T2D) pathogenesis incompletely defined. We tested hypothesis that signaling contributes to T2D. Protein abundance phosphorylation molecules were determined biopsy specimens from BMI- age-matched overweight individuals with normal glucose tolerant (NGT) T2D patients. direct lipid-induced was using...
Na,K-ATPase is a potential target for regulatory phosphorylation by protein kinase A and C (PKA PKC). To identify the sites, we have mutated alpha 1-subunit of Bufo marinus in highly conservative PKA 20 different PKC consensus sequences. The mutants were expressed Xenopus oocytes their capacity tested homogenates upon stimulation or PKC. While serine 943 (Ser-943) was identified as unique site PKA, none threonine residues are implicated phosphorylation. Controlled trypsinolysis...
We determined whether mitogen‐activated protein kinase (MAPK) and 5′‐AMP‐activated (AMPK) signalling cascades are activated in response to intense exercise skeletal muscle from six highly trained cyclists (peak O 2 uptake (V̇ O2 ,peak ) 5.14 ± 0.1 l min −1 four control subjects 3.8 matched for age body mass. Trained completed eight 5 bouts of cycling at ≈85% V̇ with 60 s recovery between work bouts. Control performed commencing the same relative , but a lower absolute intensity, comparable...
Inhibition of Na<sup>+</sup>,K<sup>+</sup>-ATPase activity by dopamine is an important mechanism which renal tubules modulate urine sodium excretion during a high salt diet. However, the molecular mechanisms this regulation are not clearly understood. in response to associated with endocytosis its α- and β-subunits, effect that protein kinase C-dependent. In study we used isolated proximal tubule cells cell line derived from opossum kidney demonstrate dopamine-induced inhibition were...
Catecholamines promote lung edema clearance via β-adrenergic-mediated stimulation of active Na + transport across the alveolar epithelium. Because epithelial type II cell -K -ATPase contributes to vectorial flux, present study was designed investigate whether undergoes acute changes in its catalytic activity response β-adrenergic-receptor stimulation. increased threefold cells incubated with 1 μM isoproterenol for 15 min, which also resulted a fourfold increase cellular levels cAMP....
We determined the muscle fiber type-specific response of intracellular signaling proteins to insulin. Epitrochlearis (Epi; 15% type I, 20% IIa, and 65% IIb), soleus (84, 16, 0%), extensor digitorum longus (EDL; 3, 57, 40%) muscles from Wistar rats were incubated without or with 120 nM insulin (3–40 min). Peak receptor (IR) tyrosine phosphorylation was reached after 6 (soleus) 20 (Epi EDL) min, sustained activity throughout exposure (40 Insulin increased substrate (IRS)-1 IRS-2...