A5064519762- Pancreatic function and diabetes
- Cell death mechanisms and regulation
- Metabolism, Diabetes, and Cancer
- Adipokines, Inflammation, and Metabolic Diseases
- Diabetes and associated disorders
- Adipose Tissue and Metabolism
- Immune Cell Function and Interaction
- Erythropoietin and Anemia Treatment
- Autophagy in Disease and Therapy
- PI3K/AKT/mTOR signaling in cancer
- Phagocytosis and Immune Regulation
- PARP inhibition in cancer therapy
- Biomarkers in Disease Mechanisms
- Cancer-related Molecular Pathways
- Mitochondrial Function and Pathology
- Epigenetics and DNA Methylation
- Diabetes Treatment and Management
- Endoplasmic Reticulum Stress and Disease
- Liver Disease Diagnosis and Treatment
- Protein Kinase Regulation and GTPase Signaling
- Immune cells in cancer
- Hormonal Regulation and Hypertension
- T-cell and B-cell Immunology
- Birth, Development, and Health
- Lipid metabolism and disorders
University Health Network
2014-2024
Toronto General Hospital
2013-2024
University of Toronto
2014-2024
Diabetes Canada
2023-2024
Sinai Health System
2021-2023
Mount Sinai Hospital
2020
Canada Research Chairs
2015-2018
John Wiley & Sons (United States)
2018
Obesity Society
2018
Toronto General Hospital Research Institute
2017
Minna Woo, Razqallah Hakem, Maria S. Soengas, Gordon Duncan, Arda Shahinian, David Kägi, Anne Mila McCurrach, Wilson Khoo, Stephen A. Kaufman, Giorgio Senaldi, Tamara Howard, Scott W. Lowe, and Tak Mak Amgen Institute Ontario Cancer Institute, Department of Medical Biophysics Immunology, University Toronto, M5G2C1, Canada; Cold Spring Harbor Laboratory, Harbor, New York 11724 USA; Amgen, Inc., Thousand Oaks, CA 91320-1789 USA
Diabetic kidney disease (DKD) is the main cause of chronic (CKD) and progresses faster in males than females. We identify sex-based differences metabolism blood metabolome male female individuals with diabetes. Primary human proximal tubular epithelial cells (PTECs) from healthy displayed increased mitochondrial respiration, oxidative stress, apoptosis, greater injury when exposed to high glucose compared PTECs Male showed glutamine fluxes TCA cycle, whereas pyruvate content. The PTEC...
Pten (phosphatase with tensin homology), a dual-specificity phosphatase, is negative regulator of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. regulates vast array biological functions including growth, metabolism, and longevity. Although PI3K/Akt pathway key determinant insulin-dependent increase in glucose uptake into muscle adipose cells, contribution this to whole-body homeostasis unclear. Here we show that muscle-specific deletion protected mice from insulin resistance...
Obesity-related insulin resistance correlates with type I interferon–driven activation and expansion of intrahepatic T cells. See the related Focus by Ma et al .
A common feature among all forms of diabetes mellitus is a functional β-cell mass insufficient to maintain euglycemia; therefore, the promotion growth and survival fundamental goal for prevention treatment. Evidence has suggested that erythropoietin (EPO) exerts cytoprotective effects on nonerythroid cells. However, influence EPO pancreatic β cells not been evaluated date. In this study, we report recombinant human treatment can protect against development in streptozotocin-induced db/db...
The mitochondrial proapoptotic protein Smac/DIABLO has recently been shown to potentiate apoptosis by counteracting the antiapoptotic function of inhibitor proteins (IAPs). In response apoptotic stimuli, Smac is released into cytosol and promotes caspase activation binding IAPs, thereby blocking their function. These observations have suggested that a new regulator apoptosis. To better understand physiological in normal cells, we generated Smac-deficient (Smac(-/-)) mice using homologous...
beta-Cell apoptosis is a key event contributing to the pathogenesis of type 1 diabetes mellitus. In addition being main mechanism by which beta cells are destroyed, beta-cell has been implicated in initiation mellitus through antigen cross-presentation mechanisms that lead beta-cell-specific T-cell activation. Caspase-3 major effector caspase involved apoptotic pathways. Despite evidence supporting importance diabetes, specific role caspase-3 this process unknown. Here, we show knockout...
Abstract Reactive oxygen species (ROS) have been linked to a wide variety of pathologies, including obesity and diabetes, but ROS also act as endogenous signalling molecules, regulating numerous biological processes. DJ-1 is one the most evolutionarily conserved proteins across species, mutations in some cases Parkinson’s disease. Here we show that maintains cellular metabolic homeostasis via modulating levels murine skeletal muscles, revealing role maintaining efficient fuel utilization. We...
Obesity-related inflammation of metabolic tissues, including visceral adipose tissue (VAT) and liver, are key factors in the development insulin resistance (IR), though many contributing mechanisms remain unclear. We show that nucleic-acid-targeting pathways downstream extracellular trap (ET) formation, unmethylated CpG DNA, or ribonucleic acids drive IR. High-fat diet (HFD)-fed mice increased release ETs VAT, decreased systemic clearance ETs, autoantibodies against conserved nuclear...
Abstract Lipid accumulation in macrophages (Mφs) is a hallmark of atherosclerosis, yet how lipid affects inflammatory responses through rewiring Mφ metabolism poorly understood. We modeled cultured wild-type mouse thioglycolate-elicited peritoneal Mφs and bone marrow–derived with conditional (Lyz2-Cre) or complete genetic deficiency Vhl, Hif1a, Nos2, Nfe2l2. Transfection studies employed RAW264.7 cells. were for 24 h oxidized low-density lipoprotein (oxLDL) cholesterol then stimulated LPS....
Abstract The accumulation of lipid and the formation macrophage foam cells is a hallmark atherosclerosis, chronic inflammatory disease. To better understand role in inflammation during atherogenesis, we studied early molecular events that follow oxidized low-density lipoprotein (oxLDL) cultured mouse macrophages. We previously showed oxLDL downregulates response conjunction with downregulation late-phase glycolysis. In this study, show within hours after LPS stimulation, macrophages...
Abstract Lipid accumulation in macrophages (Mφs) is a hallmark of atherosclerosis. Yet, how lipid loading modulates Mφ inflammatory responses remains unclear. We endeavored to gain mechanistic insights into pre-loading with free cholesterol metabolism upon LPS-induced TLR4 signaling. found that activities prolyl hydroxylases (PHDs) and factor inhibiting HIF (FIH) are higher loaded Mφs post-LPS stimulation, resulting impaired HIF-1α stability, transactivation capacity glycolysis. In RAW264.7...
Caspase-3 is essential for Fas-mediated apoptosis in vitro. We investigated the role of caspase-3 cell death vivo by injecting caspase-3-deficient mice with agonistic anti-Fas Ab. Wild-type controls died rapidly fulminant hepatitis, whereas survival caspase-3-/- was increased due to a delay hepatocyte death. Bcl-2 expression liver dramatically decreased wild-type following injection, but unchanged mice. Hepatocytes from anti-Fas-injected wild-type, not caspase-3-/-, released cytochrome c...
PTEN (phosphatase with tensin homology) is a potent negative regulator of phosphoinositide 3-kinase (PI3K)/Akt signaling, an evolutionarily conserved pathway that signals downstream growth factors, including insulin and insulin-like factor 1. In lower organisms, this participates in fuel metabolism body size regulation proteins are produced primarily by neuronal structures, whereas mammals, the major source pancreatic β cells. Recently, rodent transcription was also shown brain, particularly...
The ubiquitin-proteasome system is a key proteolytic pathway activated during skeletal muscle atrophy. proteasome, however, cannot degrade intact myofibrils or actinomyosin complexes. In rodent models of diabetes mellitus and uremia, caspase-3 involved in cleavage, generating fragments that subsequently undergo ubiquitin-proteasome-mediated degradation. Here, we demonstrate also mediates denervation-induced At 2 wk after tibial nerve transection, the denervated gastrocnemius...
Focal adhesion kinase (FAK) acts as an adaptor at the focal contacts serving a junction between extracellular matrix and actin cytoskeleton. Actin dynamics is known determinant step in insulin secretion. Additionally, FAK has been shown to regulate signaling. To investigate essential physiological role of pancreatic β-cells vivo, we generated transgenic mouse model using rat promoter (RIP)-driven Cre-loxP recombination system specifically delete β-cells. These RIPcre(+)fak(fl/fl) mice...