A5010561641- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Pancreatic function and diabetes
- Protein Kinase Regulation and GTPase Signaling
- Cancer, Hypoxia, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Polyamine Metabolism and Applications
- Cancer-related Molecular Pathways
- Cancer, Lipids, and Metabolism
- Amino Acid Enzymes and Metabolism
- Cancer-related gene regulation
- Cellular transport and secretion
- Epigenetics and DNA Methylation
- Diet and metabolism studies
- Cardiovascular Disease and Adiposity
- Regulation of Appetite and Obesity
- FOXO transcription factor regulation
- MicroRNA in disease regulation
- Ion channel regulation and function
- Thermoregulation and physiological responses
- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Diabetes and associated disorders
- Erythrocyte Function and Pathophysiology
Centre Méditerranéen de Médecine Moléculaire
2016-2025
Université Côte d'Azur
2015-2024
Inserm
2015-2024
Toxicologie, Pharmacologie et Signalisation Cellulaire
2020
Observatoire de la Côte d’Azur
2018
Centre National de la Recherche Scientifique
2014-2017
Centre for Computational Continuum Mechanics (Slovenia)
2012-2015
Institut de Pharmacologie et de Biologie Structurale
2014
Biotechnologie et Signalisation Cellulaire
2014
Hôpital l'Archet
2010
Diabetes and obesity are two metabolic diseases characterized by insulin resistance a low-grade inflammation. Seeking an inflammatory factor causative of the onset resistance, obesity, diabetes, we have identified bacterial lipopolysaccharide (LPS) as triggering factor. We found that normal endotoxemia increased or decreased during fed fasted state, respectively, on nutritional basis 4-week high-fat diet chronically plasma LPS concentration to three times, threshold defined endotoxemia....
Inflammation is associated with obesity and insulin resistance. Proinflammatory cytokines produced by adipose tissue in could alter signaling action. Recent studies have shown a relationship between IL-1beta level metabolic syndrome or type 2 diabetes. However, the ability of to action remains be explored. We demonstrated that slightly increased Glut 1 translocation basal glucose uptake 3T3-L1 adipocytes. Importantly, we found prolonged treatment reduced insulin-induced uptake, whereas an...
Abstract Metformin is a widely prescribed antidiabetic drug associated with reduced risk of cancer. Many studies show that metformin inhibits cancer cell viability through the inhibition mTOR. We recently showed antiproliferative action in prostate lines not mediated by AMP-activated protein kinase (AMPK). identified REDD1 (also known as DDIT4 and RTP801), negative regulator mTOR, new molecular target metformin. increases expression p53-dependent manner. invalidation, using siRNA or REDD1−/−...
Targeting cancer cell metabolism is a new promising strategy to fight cancer. Metformin, widely used antidiabetic agent, exerts antitumoral and antiproliferative action. In this study, the addition of metformin 2-deoxyglucose (2DG) inhibited mitochondrial respiration glycolysis in prostate cells leading severe depletion ATP. The combination two drugs was much more harmful for than treatment with or 2DG alone, 96% inhibition viability LNCaP cells. contrast, moderate effect on observed normal...
Mammalian target of rapamycin (mTOR) is a key regulator cell growth that associates with raptor and rictor to form the mTOR complex 1 (mTORC1) mTORC2, respectively. Raptor required for oxidative muscle integrity, whereas dispensable. In this study, we show muscle-specific inactivation leads severe myopathy, resulting in premature death. mTOR-deficient muscles display metabolic changes similar those observed lacking raptor, including impaired metabolism, altered mitochondrial regulation,...
In obesity, white adipose tissue (WAT) inflammation is linked to insulin resistance. Increased adipocyte chemokine (C-C motif) ligand 2 (CCL2) secretion may initiate by attracting the migration of inflammatory cells into tissue. Using an unbiased approach, we identified microRNAs (miRNAs) that are dysregulated in human obesity and assessed their possible role controlling CCL2 production. subcutaneous WAT obtained from 56 subjects, 11 miRNAs were present all subjects downregulated obesity. Of...
Treatment of cells with okadaic acid, a protein phosphatase inhibitor, leads to an insulin-resistant state without modification in the tyrosine kinase activity receptor toward exogenous substrates. In 3T3-L1 adipocytes, acid induced similar dose-dependent inhibition insulin effect on deoxyglucose uptake, phosphatidylinositol 3-kinase (PI 3-kinase) activation, and substrate (IRS) 1 phosphorylation. Simultaneously, acid-treated reduced IRS phosphorylation was linked decrease its...
To understand better the defects in proximal steps of insulin signaling during type 2 diabetes, we used differentiated human skeletal muscle cells primary culture. When compared with from control subjects, myotubes established patients diabetes presented same as those previously evidenced vivo biopsies, including defective stimulation phosphatidylinositol (PI) 3-kinase activity, decreased association PI receptor substrate (IRS)-1 and reduced IRS-1 tyrosine phosphorylation stimulation. In...
Obesity is characterized by an overgrowth of adipose tissue that leads to the formation hypoxic areas within this tissue. We investigated whether phenomenon could be responsible for insulin resistance studying effect hypoxia on signaling pathway in adipocytes.The was modulated adipocytes from human and murine origins through incubation under conditions (1% O(2)) or modulation hypoxia-inducible factor (HIF) expression. Insulin monitored phosphorylation state several key partners glucose...
Abstract Phosphatidylinositol 3-kinase (PI 3-kinase) activation promotes glucose transporter 4 (Glut 4) translocation in adipocytes. In this study, we demonstrate that protein kinase B, a serine/threonine stimulated by PI 3-kinase, is activated both insulin and okadaic acid isolated adipocytes, parallel with their effects on Glut translocation. 3T3-L1 platelet-derived growth factor as efficiently but was only half potent promoting B (PKB) activation. To look for potential role of PKB...
Obesity is characterized by the development of a low-grade chronic inflammatory state in different metabolic tissues including adipose tissue and liver. This inflammation develops response to an excess nutrient flux now recognized as important link between obesity insulin resistance. Several dietary factors like saturated fatty acids glucose well changes gut microbiota have been proposed triggers this through activation pattern-recognition receptors (PRRs), Toll-like (TLR), inflammasome,...
Apelin, an adipocyte-secreted factor upregulated by insulin, is increased in adipose tissue (AT) and plasma with obesity. Apelin was recently identified as a new player the control of glucose homeostasis. However, regulation apelin APJ (apelin receptor) expression skeletal muscle relation to insulin resistance or type 2 diabetes not known. Thus we studied AT different mice models obesity diabetic patients. In insulin-resistant high-fat (HF)-fed mice, were compared control. This case highly...
Activation of the p53 pathway in adipose tissue contributes to insulin resistance associated with obesity. However, mechanisms activation and effect on adipocyte functions are still elusive. Here we found a higher level DNA oxidation reduction telomere length mice fed high-fat diet an increase damage adipocytes. Interestingly, hallmarks chronic visible at onset Furthermore, injection lean doxorubicin, damage-inducing drug, increased expression chemokines promoted its infiltration by...
Insulin stimulation of glucose transport involves the translocation vesicles containing transporter Glut 4 to plasma membrane. Rab proteins, which have been implicated in regulation vesicular traffic, were studied adipocytes. Rab3B, Rab3C, Rab4, and Rab8 detected, but Rab3A was not. In absence insulin, Rab3B Rab3C cytosolic, while Rab4 associated with membranes. Only distribution modified by insulin. unstimulated adipocytes, most found a low density microsomal fraction, also contained...