A5029750922- Chronic Kidney Disease and Diabetes
- Oral Health Pathology and Treatment
- Renal Diseases and Glomerulopathies
- Oral microbiology and periodontitis research
- Atherosclerosis and Cardiovascular Diseases
- Amino Acid Enzymes and Metabolism
- Neuroendocrine regulation and behavior
- Stress Responses and Cortisol
- Dermatological and Skeletal Disorders
- Parathyroid Disorders and Treatments
- Immune Response and Inflammation
- Circadian rhythm and melatonin
- Adipokines, Inflammation, and Metabolic Diseases
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Diabetes and associated disorders
- Adipose Tissue and Metabolism
- Cardiovascular Disease and Adiposity
- Mitochondrial Function and Pathology
- Pancreatitis Pathology and Treatment
- Cancer, Hypoxia, and Metabolism
- Eicosanoids and Hypertension Pharmacology
- Systemic Lupus Erythematosus Research
- Proteoglycans and glycosaminoglycans research
- Cerebrovascular and Carotid Artery Diseases
- Dialysis and Renal Disease Management
Joslin Diabetes Center
2017-2023
Harvard University
2017-2023
Fukuoka University
2020
Hôtel-Dieu de Québec
2014
Inserm
2011-2014
Sorbonne Université
2011-2014
Neurosciences Paris-Seine
2014
Centre National de la Recherche Scientifique
2014
Université Paris Cité
2014
Centre hospitalier universitaire de Québec
2014
BACKGROUND Vascular calcification, a regulated process in chronic kidney disease (CKD), requires vascular smooth muscle cell (VSMC) differentiation into osteoblast-like cells. This phenomenon can be enhanced by inflammatory cytokines and production of reactive oxygen species (ROS). In CKD rats with we investigated whether cytokines, ROS generation, downstream signaling events are associated CKD-related calcification. METHODS was induced male Wistar renal mass ablation calcification high...
OBJECTIVE Elevated glycolytic enzymes in renal glomeruli correlated with preservation of function the Medalist Study, individuals ≥50 years type 1 diabetes. Specifically, pyruvate kinase M2 (PKM2) activation protected insulin-deficient diabetic mice from hyperglycemia-induced glomerular pathology. This study aims to extend these findings a separate cohort and 2 diabetes discover new circulatory biomarkers for protection through proteomics metabolomics Medalists’ plasma. We hypothesize that...
Insulin resistance and hyperglycemia are risk factors for periodontitis poor wound healing in diabetes, which have been associated with selective loss of insulin activation the PI3K/Akt pathway gingiva. This study showed that mouse gingiva due to deletion smooth muscle fibroblast receptor (SMIRKO mice) or systemic metabolic changes induced by a high-fat diet (HFD) HFD-fed mice exacerbated periodontitis-induced alveolar bone loss, preceded delayed neutrophil monocyte recruitment impaired...
Diabetic nephropathy (DN) arises from systemic and local changes in glucose metabolism hemodynamics. We have reported that many glycolytic mitochondrial enzymes, such as pyruvate kinase M2 (PKM2), were elevated renal glomeruli of DN-protected patients with type 1 2 diabetes. Here, mice PKM2 overexpression specifically podocytes (PPKM2Tg) generated to uncover the protective function PPKM2Tg a potential therapeutic target prevented albumin/creatinine ratio (ACR), mesangial expansion, basement...
Insulin resistance (IR) can increase atherosclerotic and cardiovascular risk by inducing endothelial dysfunction, decreasing nitric oxide (NO) production, accelerating arterial inflammation. The aim is to determine the mechanism which insulin action NO production in cells improve systemic bioenergetics decrease atherosclerosis via differentiation of perivascular progenitor (PPCs) into brown adipocytes (BAT).Studies used various transgenic deletion mutant ApoE-/- mice receptors, eNOS...
The objective of this study is to evaluate whether exogenously induced hyperinsulinemia may increase the development atherosclerosis.Hyperinsulinemia, by exogenous insulin implantation in high-fat fed (60% fat HFD) apolipoprotein E-deficient mice (ApoE-/-) mice, exhibited resistance, hyperglycemia, and hyperinsulinemia. Atherosclerosis was measured accumulation fat, macrophage, extracellular matrix aorta. After 8 weeks on HFD, ApoE-/- were subcutaneously implanted with control (sham) or...
Free radicals, or reactive oxygen species (ROS), are highly byproducts of degradation. They well known for their cellular toxicity, but few studies have analyzed potential role in homeostatic processes. We investigated ROS production and function during the arginine vasopressin (AVP) hypothalamic response to hyperosmolarity. Six-week-old male C3H/HeJ mice were subjected salt loading 2 8 d. The osmotic axis was progressively activated reached a new steady-state status at d as demonstrated by...
Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes (T1D). A pro-calcific drift circulating monocytes has been linked to vascular calcification and marked by the surface expression osteocalcin (OCN). We studied OCN+ unique population with ≥50 years T1D, 50-Year Joslin Medalists (J50M). CD45 bright/CD14+/OCN+ cells mononuclear blood cell fraction were quantified flow cytometry reported as percentage bright cells. Mechanisms inducing OCN human vitro. Subjects without...
We have reported that up-regulation of PKM2 in renal glomeruli isolated from patients with more than 50 years type 1 diabetes (Joslin Medalist Study) correlated preservation function even the presence chronic hyperglycemia. Further, pharmacological activation T1D mice and podocyte-specific deletion cultured cells vivo strongly showed protects hyperglycemia/diabetes induced damage (Nat. Med 2017). To confirm these findings 2 diabetes, we performed following: 1. protein expressions glycolytic...
Clinical studies have suggested that loss of insulin’s action and excessive IGF-1 levels in the glomeruli elevate risk for diabetic kidney disease (DKD). To define potential pathogenic role insulin signaling DKD, we generated mice with selective receptor (IR) or (IGF-1R) mesangial cells (MCs) by cross breeding IRflox/flox Sm22α-Cre (SMIRKO) IGF-1Rflox/flox Myh11-Cre (SMIGF1RKO), examined urinary albumin excretion (ACR) expansion 6 month duration streptozotocin (STZ)-induced diabetes. were...
Activation of brown adipose tissue (BAT) has been shown to decrease atherosclerosis due its systemic actions improve insulin sensitivity and facilitate weight loss. However, the direct effect BAT cytokines on vascular arterial function not studied. We have reported that enhancing insulin’s action endothelial cells (EC) by overexpressing IRS1 EC ApoE-/- background (ECIRS1/ApoE-/- mice) greatly increased induced NO production decreased atherosclerosis. ECIRS1 mice exhibited significant...
A major cause of poor wound healing and periodontitis in diabetes is defective immune response to infections. Insulin signaling via the PI3K/Akt pathway selectively inhibited gingival fibroblasts diabetic rodents patients. To determine how loss insulin actions can affect development, myofibroblast receptors (IR) were deleted by crossbreeding IRβ-flox/flox mice with SM22-Cre C57BL/6 (SMIRKO) mice, which fed regular diet (RD), while wild type (WT) littermates high-fat (HFD) for 10 weeks....
Diabetic nephropathy (DN) is the result of abnormal systemic and local changes in metabolism hemodynamics. We have reported that many glycolytic enzymes, such as pyruvate kinase M2 (PKM2), were elevated renal glomeruli type 1 2 diabetic patients who protected from DN. TEPP46, a small-molecule which activates PKM2 by inducing oligomerization, reversed glomerular pathology mice. After 7 months STZ induced diabetes, mice with specific overexpression podocytes (PPKM2Tg) podocin promoter,...
<p> </p> <p>Insulin resistance and hyperglycemia are risk factors for periodontitis poor wound healing in diabetes, which have been associated with selective loss of insulin- activation the PI3K/Akt pathway gingiva. This study showed that insulin mouse gingiva due to deletion smooth muscle fibroblast receptor (SMIRKO mice) or systemic metabolic changes induced by high fat diet (HFD) HFD-fed mice exacerbated periodontitis-induced alveolar bone loss, preceded delayed...
<p> </p> <p>Insulin resistance and hyperglycemia are risk factors for periodontitis poor wound healing in diabetes, which have been associated with selective loss of insulin- activation the PI3K/Akt pathway gingiva. This study showed that insulin mouse gingiva due to deletion smooth muscle fibroblast receptor (SMIRKO mice) or systemic metabolic changes induced by high fat diet (HFD) HFD-fed mice exacerbated periodontitis-induced alveolar bone loss, preceded delayed...
Elevated expression of pyruvate kinase isoform M2 (PKM2) in the renal glomeruli people with diabetes is associated protection from nephropathy even hyperglycemia. Furthermore, systemic use PKM2 activators (TEPP46) can prevent or reverse glomerular pathology diabetic mice. To determine specifically role development progression glomerulopathy, we generated transgenic mice overexpressing specific targeted to podocytes (PPKM2Tg mice) driven by podocin promoter. Analysis these showed 1.5-fold...
Although metabolic risk factors that accelerate atherosclerosis are shared between people with type 1 (T1D) and 2 (T2D) diabetes, it remains unknown whether autoimmunity in T1D contribute to cardiovascular pathologies, which have been reported for other autoimmune diseases. In order determine the role of without overt we generated ApoE deficient NOD (ApoE-/--NOD) mice by CRISPR/Cas9 gene editing. The ApoE-/- spontaneously developed diabetes atherosclerosis. We also congenic ApoE-/--NOD do...
Diabetic nephropathy (DN) is the result of systemic and local changes in metabolism hemodynamics. We have found that elevation glycolytic enzymes, such as pyruvate kinase M2 (PKM2) renal glomeruli correlated with preservation function human type 1 2 diabetes. A small-molecule PKM2 activator, TEPP46, prevented or reversed glomerular pathology diabetic mice chronic duration. Mice overexpression specifically podocytes (PPKM2Tg) were generated, which after 7 months diabetes induced by...
Hyperglycemia, hyperlipidemia and hypertension have been evaluated extensively as risk factors for cardiovascular disease (CVD) in people with type 1 diabetes (T1DM). However, the impact of autoimmunity T1DM on CVD has not determined. We generated several mice models atherosclerosis including ApoE-/-/NOD, ApoE-/-/NOD (congenic non non-autoimmune), (autoimmunity insulitis, nondiabetes) autoimmune diabetic mice. All groups high plasma lipids but only had hyperglycemia. (insulitis diabetes)...
Mitochondrial abnormalities induced by diabetes have been postulated to cause several complications including nephropathy. Elevated expressions of enzymes for glycolysis and mitochondrial functions in the glomeruli associated with protection against development diabetic nephropathy chronic duration. Activation a glycolytic enzyme, pyruvate kinase M2 (PKM2), small molecule selective activator (TEPP-46) or its targeted overexpression podocytes mice reversed glomerular dysfunction pathology...
Vascular smooth muscle cells (VSMCs) play an important role in the development of stability atherosclerotic plaque. We reported that knockout insulin receptor (IR), but not IGF1 receptor, VSMCs reduced intimal hyperplasia femoral artery after wire injury. To investigate IR on plaque, ApoE and double (SMIRKO/ApoE-/-) mice were generated. Extent lipid deposition atherosclerosis increased aorta SMIRKO/ApoE-/- compared to control (p&lt;0.05). However, total cell numbers proliferation VSMCs,...