Concept

Insulin signal transduction pathway

Publications associées (29)

Drug Screening in C. elegans to identify new pharmacological mitochondrial stress inducers

Mitochondria are essential organelles participating in numerous cellular functions, including energy harvesting, regulation of homeostasis and apoptosis. Changes in mitochondrial number, morphology, and function not only impact cellular metabolism but also ...

EPFL2024

AMP-activated Protein Kinase (AMPK): New molecular insights and novel downstream targets

Katyayanee Neopane

AMP-activated Protein Kinase (AMPK) is a central regulator of energy homeostasis and a promising drug target for metabolic disorders. It exists as complexes of three subunits, a catalytic alpha, and two regulatory beta and gamma subunits. The regulation of ...

EPFL2022

Inositol pyrophosphates promote the interaction of SPX domains with the coiled-coil motif of PHR transcription factors to regulate plant phosphate homeostasis

Luciano Andres Abriata

Phosphorus is an essential nutrient taken up by organisms in the form of inorganic phosphate (Pi). Eukaryotes have evolved sophisticated Pi sensing and signaling cascades, enabling them to stably maintain cellular Pi concentrations. Pi homeostasis is regul ...

Nature Research2021

Multipotent mesenchymal stromal cells derived from porcine exocrine pancreas improve insulin secretion from juvenile porcine islet cell clusters

Sandrine Gerber, Luca Szabó

Neonatal and juvenile porcine islet cell clusters (ICC) present an unlimited source for islet xenotransplantation to treat type 1 diabetes patients. We isolated ICC from pancreata of 14 days old juvenile piglets and characterized their maturation by immuno ...

2021

The ULK1/2 and AMPK Inhibitor SBI-0206965 Blocks AICAR and Insulin-Stimulated Glucose Transport

Jonas Roland Knudsen

The small molecule kinase inhibitor SBI-0206965 was originally described as a specific inhibitor of ULK1/2. More recently, it was reported to effectively inhibit AMPK and several studies now report its use as an AMPK inhibitor. Currently, we investigated t ...

2020

Prior exercise in humans redistributes intramuscular GLUT4 and enhances insulin -stimulated sarcolemmal and endosomal GLUT4 translocation

Jonas Roland Knudsen

Objective: Exercise is a cornerstone in the management of skeletal muscle insulin-resistance. A well-established benefit of a single bout of exercise is increased insulin sensitivity for hours post-exercise in the previously exercised musculature. Although ...

2020

Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans

Johan Auwerx, Richardus Houtkooper

Background: Nicotinamide riboside (NR) is an NAD(+) precursor that boosts cellular NAD(+) concentrations. Preclinical studies have shown profound metabolic health effects after NR supplementation. ...

OXFORD UNIV PRESS2020

Growth differentiation factor 15 protects against the aging-mediated systemic inflammatory response in humans and mice

Johan Auwerx, Jun Yong Kim, Dongryeol Ryu, Ludger Jan Elzuë Goeminne

Mitochondrial dysfunction is associated with aging-mediated inflammatory responses, leading to metabolic deterioration, development of insulin resistance, and type 2 diabetes. Growth differentiation factor 15 (GDF15) is an important mitokine generated in r ...

2020

N-acetylaspartate availability is essential for juvenile survival on fat-free diet and determines metabolic health

Johan Auwerx, Dina Hofer

N-acetylaspartate (NAA) is synthesized by aspartate N-acetyltransferase (gene: Nat8l) from acetyl-coenzyme A and aspartate. In the brain, NAA is considered an important energy metabolite for lipid synthesis. However, the role of NAA in peripheral tissues r ...

2019

High frequency shift in Carotid Sinus Nerve and Sympathetic Nerve activity in Type 2 Diabetic Rat Model

Silvestro Micera

Overactivity of the sympathetic nervous system (SNS) is associated to several cardiovascular and metabolic dysfunctions, such as hypertension and insulin resistance. Indirect biochemical measurements and surgical manipulations have provided preliminary evi ...

IEEE2019

Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage

Carlos Canto Alvarez, Joanna Ratajczak, Miriam Valera Alberni

Supplementation with the NAD(+) precursor nicotinamide riboside (NR) ameliorates and prevents a broad array of metabolic and aging disorders in mice. However, little is known about the physiological role of endogenous NR metabolism. We have previously show ...

Nature Research2019

Anti-fibrotic effect of ketoprofen-grafted alginate microcapsules in the transplantation of insulin producing cells

Sandrine Gerber, Daniel Ortiz Trujillo, François Rémi Pierre Noverraz, Luca Szabó

The controlled release of small molecular modulators of the immune response from hydrogel microspheres (MS) used for cell immobilization is an attractive approach to reduce pericapsular fibrotic overgrowth (PFO) after transplantation. Ketoprofen is a well- ...

2018

A systems perspective on brown adipogenesis and metabolic activation

Bart Deplancke, Magda Zachara, Rachana Narendra Pradhan

Brown adipocytes regulate energy expenditure via mitochondrial uncoupling. This makes these fat cells attractive therapeutic targets to tackle the burgeoning issue of obesity, which itself is coupled to insulin resistance, type 2 diabetes, cardiovascular a ...

Wiley-Blackwell2017

Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis

Johan Auwerx, Dongryeol Ryu

Reduced mitochondria! electron transport chain activity promotes longevity and improves energy homeostasis via cell-autonomous and non-autonomous factors in multiple model systems. This mitohormetic effect is thought to involve the mitochondrial unfolded p ...

Rockefeller University Press2017

The NAD(+)-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytes

Vera Monica Lemos Da Silva

Insulin resistance is a major predictor of the development of metabolic disorders. Sirtuins (SIRTs) have emerged as potential targets that can be manipulated to counteract age-related diseases, including type 2 diabetes. SIRT2 has been recently shown to ex ...

Oxford University Press2017

A multiscale study of the role of dynamin in the regulation of glucose uptake

Martinus Adela Maria Gijs, Johan Auwerx, Kristina Schoonjans, Laurent Mouchiroud, Raphaël Etienne Jean Trouillon, Keir Joe Menzies, Maria Cristina Letizia

Glucose uptake in muscle cells in response to insulin is a fundamental mechanism for metabolism. The inability of cells to mobilize the specific glucose transporter GLUT4 is believed to be at least partially accountable for diseases, like diabetes, where c ...

Royal Soc Chemistry2017

Multipotent mesenchymal stromal cells enhance insulin secretion from human islets via N-Cadherin interaction and prolong function of transplanted encapsulated islets in mice

Jutta Christine Wandrey, Sandrine Gerber, Redouan Mahou

Background: Multipotent mesenchymal stromal cells (MSC) enhance viability and function of islets of Langerhans. We aimed to examine the interactions between human MSC and human islets of Langerhans that influence the function of islets. Methods: Human MSC ...

Biomed Central Ltd2017

Label-free fast 3D coherent imaging reveals pancreatic islet micro-vascularization and dynamic blood flow

Theo Lasser, Anne Grapin-Botton, Daniel Pawel Szlag, Arno Pino Bouwens, Jérôme Extermann, Corinne Berclaz, Paul James Marchand, David Nguyen

In diabetes, pancreatic beta-cells play a key role. These cells are clustered within structures called islets of Langerhans inside the pancreas and produce insulin, which is directly secreted into the blood stream. The dense vascularization of islets of La ...

2016

SIRT1 Gain of Function Does Not Mimic or Enhance the Adaptations to Intermittent Fasting

Carlos Canto Alvarez, Patrick Descombes

Caloric restriction (CR) has been shown to prevent the onset of insulin resistance and to delay age-related physiological decline in mammalian organisms. SIRT1, a NAD(+) -dependent deacetylase enzyme, has been suggested to mediate the adaptive responses to ...

Elsevier2016

Dietary restriction and Sirtuin 1 in metabolic health: connections and divergences

Carlos Canto Alvarez

Aging is the major risk factor for a constellation of multifactorial diseases, including insulin resistance, diabetes and cardiovascular complications. Dietary restriction has been shown to delay or prevent the manifestation of age-related health decline, ...

Cambridge Univ Press2016