A5040013861- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Advanced Proteomics Techniques and Applications
- Pancreatic function and diabetes
- Muscle metabolism and nutrition
- Muscle Physiology and Disorders
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Redox biology and oxidative stress
- Sirtuins and Resveratrol in Medicine
- Mass Spectrometry Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Diet and metabolism studies
- Adipokines, Inflammation, and Metabolic Diseases
- Glycogen Storage Diseases and Myoclonus
- Autophagy in Disease and Therapy
- Regulation of Appetite and Obesity
- Cellular transport and secretion
- Biochemical Analysis and Sensing Techniques
University of Copenhagen
2019-2024
Novo Nordisk Foundation
2021-2024
Novo Nordisk Foundation Center for Basic Metabolic Research
2021
Foundation Center
2021
Abstract Skeletal muscle conveys several of the health-promoting effects exercise; yet underlying mechanisms are not fully elucidated. Studying skeletal is challenging due to its different fiber types and presence non-muscle cells. This can be circumvented by isolation single fibers. Here, we develop a workflow enabling proteomics analysis pools isolated fibers from freeze-dried human biopsies. We identify more than 4000 proteins in slow- fast-twitch Exercise training alters expression 237...
Exercise is an effective strategy in the prevention and treatment of metabolic diseases. Alterations skeletal muscle proteome, including post-translational modifications, regulate its adaptations to exercise. Here, we examined effect high-intensity interval training (HIIT) on proteome acetylome human muscle, revealing response 3168 proteins 1263 lysine acetyl-sites 464 acetylated proteins. We identified global protein exercise involved metabolism, excitation-contraction coupling,...
Muscle insulin sensitivity for stimulating glucose uptake is enhanced in the period after a single bout of exercise. We recently demonstrated that AMPK necessary AICAR, contraction, and exercise to enhance muscle whole-body mice. Correlative observations from both human rodent skeletal suggest regulation phosphorylation status TBC1D4 may relay this sensitization. However, necessity phenomenon has not been proven. Thus, purpose study was determine whether enhancing response AICAR contraction....
Evidence for AMP-activated protein kinase (AMPK)-mediated regulation of skeletal muscle metabolism during exercise is mainly based on transgenic mouse models with chronic (lifelong) disruption AMPK function. Findings such are potentially biased by secondary effects related to a lack To study the direct effect(s) exercise, we generated new model inducible muscle-specific deletion AMPKα catalytic subunits in adult mice.Tamoxifen-inducible and AMPKα1/α2 double KO mice (AMPKα imdKO) were using...
Human genome-wide association studies (GWAS) suggest a functional role for central glutamate receptor signaling and plasticity in body weight regulation. Here, we use UK Biobank GWAS summary statistics of mass index (BMI) fat percentage (BF%) to identify genes encoding proteins known interact with postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) N -methyl- d -aspartate (NMDA) receptors. Loci in/near discs large homolog 4 ( DLG4 ) protein interacting C kinase 1 PICK1...
The ability of insulin to stimulate glucose uptake in skeletal muscle is important for whole-body glycemic control. Insulin-stimulated improved the period after a single bout exercise, and accumulating evidence suggests that phosphorylation TBC1D4 by protein kinase AMPK primary mechanism responsible this phenomenon. To investigate this, we generated knock-in mouse model with serine-to-alanine point mutation at residue 711 phosphorylated response both activation. Female TBC1D4-S711A mice...
White adipose tissue (WAT) is important for metabolic homeostasis. We established the differential proteomic signatures of WAT in glucose-tolerant lean and obese individuals patients with type 2 diabetes (T2D) response to 8 weeks high-intensity interval training (HIIT). Using a high-throughput reproducible mass spectrometry–based proteomics pipeline, we identified 3773 proteins found that most regulated displayed progression markers dysfunctional from T2D were highly associated clinical...
The AMP-activated protein kinase (AMPK) gets activated in response to energetic stress such as contractions and plays a vital role regulating various metabolic processes insulin-independent glucose uptake skeletal muscle. main upstream that activates AMPK through phosphorylation of α-AMPK Thr172 muscle is LKB1, however some studies have suggested Ca2+/calmodulin-dependent 2 (CaMKK2) acts an alternative activate AMPK. We aimed establish whether CaMKK2 involved activation promotion following A...
Abstract Highlights Advanced proteomics analysis reveals personalized signatures of insulin resistance Fasting muscle proteome and phosphoproteome predicts whole-body sensitivity Insulin-stimulated selective Phosphoproteome atlas explains sex-specific metabolism Graphical Insulin is a hallmark type 2 diabetes, which highly heterogeneous disease with diverse pathology. Understanding the molecular its association individual phenotypic traits crucial for advancing precision medicine in...
A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22015-4
Skeletal muscle is an insulin-responsive tissue and typically takes up most of the glucose that enters blood after a meal. Moreover, it has been reported skeletal may increase extraction from by to 50-fold during exercise compared resting conditions. The in uptake insulin stimulation dependent on translocation transporter 4 (GLUT4) intracellular compartments cell surface membrane, as well phosphorylation glucose-6-phosphate hexokinase II. Isolation incubation mouse muscles such m. soleus...
Insulin-stimulated muscle glucose uptake is a key process in glycemic control. This depends on the redistribution of transporters to surface membrane, that involves regulatory proteins such as TBC1D1 and TBC1D4. Accordingly, TBC1D4 loss-of-function mutation human skeletal associated with an increased risk type 2 diabetes, observations from carriers variant associate this protein severe obesity phenotype. Here, we identified interactors endogenous by unbiased proteomics approach. We detected...
Skeletal muscle is an insulin-responsive tissue and typically takes up most of the glucose that enters blood after a meal. Moreover, it has been reported skeletal may increase extraction from by to 50-fold during exercise compared resting conditions. The in uptake insulin stimulation dependent on translocation transporter 4 (GLUT4) intracellular compartments cell surface membrane, as well phosphorylation glucose-6-phosphate hexokinase II. Isolation incubation mouse muscles such m. soleus...
Summary Metformin is an inexpensive oral anti-hyperglycemic agent used worldwide as a first-choice drug for the prevention of type 2 diabetes mellitus (T2DM). Although current view suggests that metformin exerts its effect by lowering hepatic glucose production, it has been proposed also reduce hyperglycemia increasing uptake in skeletal muscle via activation AMP-activated protein kinase (AMPK). Herein, we demonstrate lean and diet-induced obese (DIO) male female mouse models occurs...
Exercise is an effective strategy in the prevention and treatment of metabolic diseases. Alterations skeletal muscle proteome, including post-translational modifications, regulate its adaptations to exercise. Here, we examined effect high-intensity interval training (HIIT) on proteome acetylome human muscle, revealing response 3168 proteins 1263 lysine acetyl-sites 464 acetylated proteins. We identified global protein exercise involved metabolism, excitation-contraction coupling,...
Abstract Skeletal muscle regulates glucose uptake in response to insulin and exercise which is critical for maintaining metabolic health. We conducted a comprehensive phosphoproteomic analysis of skeletal from healthy people an acute bout or stimulation by hyperinsulinemic euglycemic clamp. Our revealed 233 phosphosites regulated both most were opposite directions. However, 71 on 55 proteins displayed regulation the same direction, indicating potential convergence signaling pathways....
Insulin-stimulated muscle glucose uptake is a key process in glycemic control. This depends on the redistribution of transporters to surface membrane, which involves regulatory proteins such as TBC1D1 and TBC1D4. Accordingly, TBC1D4 loss-of-function mutation human skeletal associated with increased risk type 2 diabetes, observations from carriers variant associate this protein severe obesity phenotype. Here, we identified interactors endogenous by an unbiased proteomics approach. We detected...
Insulin-stimulated muscle glucose uptake is a key process in glycemic control. This depends on the redistribution of transporters to surface membrane, which involves regulatory proteins such as TBC1D1 and TBC1D4. Accordingly, TBC1D4 loss-of-function mutation human skeletal associated with increased risk type 2 diabetes, observations from carriers variant associate this protein severe obesity phenotype. Here, we identified interactors endogenous by an unbiased proteomics approach. We detected...