A5019728361- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Muscle Physiology and Disorders
- Pancreatic function and diabetes
- Muscle metabolism and nutrition
- Exercise and Physiological Responses
- interferon and immune responses
- Peroxisome Proliferator-Activated Receptors
- Diet and metabolism studies
- Estrogen and related hormone effects
- Mesenchymal stem cell research
- Cardiovascular Function and Risk Factors
- Autophagy in Disease and Therapy
- RNA regulation and disease
- Mitochondrial Function and Pathology
- PI3K/AKT/mTOR signaling in cancer
- Epigenetics and DNA Methylation
- Protein Kinase Regulation and GTPase Signaling
- Tissue Engineering and Regenerative Medicine
- NF-κB Signaling Pathways
- Telomeres, Telomerase, and Senescence
- Immune cells in cancer
- Menopause: Health Impacts and Treatments
- Effects of Environmental Stressors on Livestock
- Endoplasmic Reticulum Stress and Disease
Indiana University – Purdue University Indianapolis
2020-2025
Indiana University School of Medicine
2020-2024
Indiana University
2023-2024
University School
2024
Indiana Hemophilia and Thrombosis Center
2023
East Carolina University
2013-2022
Indiana Biosciences Research Institute
2020
Brigham and Women's Hospital
2005-2010
Harvard University
2005-2010
Joslin Diabetes Center
2005-2010
Insulin and contraction increase GLUT4 translocation in skeletal muscle via distinct signaling mechanisms. Akt substrate of 160 kDa (AS160) mediates insulin-stimulated L6 myotubes, presumably through activation Akt. Using vivo, vitro, situ methods, insulin, contraction, the AMP-activated protein kinase (AMPK) activator AICAR all increased AS160 phosphorylation mouse muscle. Insulin-stimulated was fully blunted by wortmannin vitro Akt2 knockout (KO) mice vivo. In contrast,...
Studies in nonmuscle cells have demonstrated that Ca(2+)/calmodulin-dependent protein kinase kinases (CaMKKs) are upstream regulators of AMP-activated (AMPK) and Akt. In skeletal muscle, activation AMPK Akt has been implicated the regulation glucose uptake. The objective this study was to determine whether CaMKKalpha regulates muscle uptake, it is dependent on and/or activation. Expression vectors containing constitutively active (caCaMKKalpha) or empty vector were transfected into mouse...
Nuclear factor-κB (NF-κB) is a transcription factor with important roles in regulating innate immune and inflammatory responses. NF-κB activated through the phosphorylation of its inhibitor, IκB, by IκB kinase (IKK) complex. Physical exercise elicits changes skeletal muscle gene expression, yet signaling cascades factors involved remain largely unknown. To determine whether regulated vivo, rats were run on motorized treadmill for 5–60 min. Exercise resulted up to twofold increases IKKα/β...
TBC1D4 (also known as AS160) regulates glucose transporter 4 (GLUT4) translocation and uptake in adipocytes skeletal muscle. Its mode of action involves phosphorylation serine (S)/threonine (T) residues by upstream kinases resulting inactivation Rab-GTPase-activating protein (Rab-GAP) activity leading to GLUT4 mobilization. The majority sites on lie within the Akt consensus motif are phosphorylated insulin stimulation. However, 5′-AMP-activated kinase (AMPK) other may also phosphorylate...
Studies using chemical inhibitors have suggested that the Ca 2+ -sensitive serine/threonine kinase /calmodulin-dependent protein II (CaMKII) is a key regulator of both insulin- and contraction-stimulated glucose uptake in skeletal muscle. However, due to nonspecificity these inhibitors, specific role CaMKII may play regulation not known. We sought determine whether inhibition impairs and/or contraction-induced mouse Expression vectors containing green fluorescent conjugated inhibitory...
Insulin and contraction are potent stimulators of GLUT4 translocation increase skeletal muscle glucose uptake. We recently identified the Rab GTPase-activating protein (GAP) AS160 as a putative point convergence linking distinct upstream signaling cascades induced by insulin in mouse muscle. Here, we studied functional implications these events using an vivo electroporation technique to overexpress wild type three mutants tibialis anterior muscles: 1) mutated prevent phosphorylation on four...
Muscle-specific RING finger-1 (MuRF-1), a ubiquitin ligase and key regulator of proteasome-dependent protein degradation, is highly expressed during skeletal muscle atrophy. The transcription factor forkhead box O3 (FoxO3) induces MuRF-1 expression, but the direct role other major atrophy-related factors, such as SMAD3, largely unknown. goal this study was to determine whether SMAD3 individually regulates, or with FoxO3 coordinately expression. In cultured myotubes human embryonic kidney...
GLUT4 is necessary for acute insulin- and contraction-induced skeletal muscle glucose uptake, but its role in chronic loading (overload)-induced uptake unknown. Our goal was to determine whether required overload-induced uptake. Overload induced mouse plantaris by unilateral synergist ablation. After 5 days, weights ex vivo [3H]-2-deoxy-d-glucose were assessed. Overload-induced hypertrophic growth not impaired muscle-specific knockout mice, demonstrating that these processes. To assess which...
Insulin and contraction increase skeletal muscle glucose uptake through distinct additive mechanisms. However, recent reports have demonstrated that both signals converge on the Akt substrate of 160 kDa (AS160), a protein regulates GLUT4 translocation. Although AS160 phosphorylation is believed to be primary factor affecting its activity, also possesses calmodulin-binding domain (CBD). This raises possibility contraction-stimulated increases in Ca(2+)/calmodulin could modulate function.To...
Objective Whole‐body protein metabolism is dysregulated with obesity. The goal of the study was to determine whether activity and expression major degradation pathways are compromised specifically in human skeletal muscle Methods Primary (HSkM) cell cultures were utilized since cellular mechanisms can be studied absent hormones contractile that could independently influence metabolism. HSkM from 10 lean women (BMI ≤ 26.0 kg/m 2 ) 8 severe obesity ≥ 39.0) examined basally when stimulated...
The ability to increase fatty acid oxidation (FAO) in response dietary lipid is impaired the skeletal muscle of obese individuals, which associated with a failure coordinately upregulate genes involved FAO. While molecular mechanisms contributing this metabolic inflexibility are not evident, possible candidate carnitine palmitoyltransferase-1B (CPT1B), rate-limiting step present study was undertaken determine if differential CPT1B gene transcription between lean and severely subjects linked...
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...
Hyperuricemia is implicated in numerous pathologies, but the mechanisms underlying uric acid production are poorly understood. Using a combination of mouse studies, cell culture and human serum samples, we sought to determine cellular source acid. In mice, fasting glucocorticoid treatment increased release from ex vivo-incubated skeletal muscle. vitro, glucocorticoids transcription factor FoxO3 purine nucleotide degradation differentiated muscle cells, which coincided with transcriptional...
A short-term high-fat diet impairs mitochondrial function and the ability of skeletal muscle to respond growth stimuli, but it is unknown whether such a alters atrophy signals. The purpose this study was determine rapid weigh gain induced by (HF) accelerates denervation-induced atrophy.Adult, male mice (C57BL/6) were fed control or HF (60 % calories as fat) for 3 weeks (3wHF). Sciatic nerve sectioned unilaterally final 5 14 days diet. Soleus extensor digitorum longus (EDL) muscles removed...
The skeletal muscle of obese individuals exhibits an impaired ability to increase the expression genes linked with fatty acid oxidation (FAO) upon lipid exposure. present study determined if this response could be attributed differential DNA methylation signatures. RNA and were isolated from primary human cells (HSkMC) lean severely women following incubation. mRNA quantified for that globally regulate FAO [PPARγ coactivator (PGC-1α), peroxisome proliferator-activated receptors (PPARs),...
Aerobic exercise training is known to have profound cardioprotective effects in disease, yet cellular mechanisms remain largely undefined. We tested the hypothesis that increased sarcoplasmic reticulum Ca 2+ buffering and voltage-gated channel density underlie coronary smooth muscle intracellular (Ca i ) dysregulation diabetic dyslipidemia would prevent these increases. Yucatan swine were maintained 1) control, 2) alloxan-induced hyperglycemic, 3) high fat/cholesterol fed, 4) hyperglycemic...