Publications associées à Biochemical quantification of total brain glycogen concentration in rats under different glycemic states

SLC25A46 promotes mitochondrial fission and mediates resistance to lipotoxic stress in INS-1E insulin-secreting cells

Glucose sensing in pancreatic D-cells depends on oxidative phosphorylation and mitochondria-derived signals that promote insulin secretion. Using mass spectrometry-based phosphoproteo-mics to search for downstream effectors of glucose-dependent signal tran ...

COMPANY BIOLOGISTS LTD2023

Microtubule-mediated GLUT4 trafficking is disrupted in insulin-resistant skeletal muscle

Martinus Gijs, Raphaël Etienne Jean Trouillon, Martin Rainer Wohlwend

Microtubules serve as tracks for long-range intracellular trafficking of glucose transporter 4 (GLUT4), but the role of this process in skeletal muscle and insulin resistance is unclear. Here, we used fixed and live-cell imaging to study microtubule-based ...

eLIFE SCIENCES PUBL LTD2023

Type 2 diabetes disrupts circadian orchestration of lipid metabolism and membrane fluidity in human pancreatic islets

Howard Riezman, Jonathan Paz Montoya

Recent evidence suggests that circadian clocks ensure temporal orchestration of lipid homeostasis and play a role in pathophysiology of metabolic diseases in humans, including type 2 diabetes (T2D). Nevertheless, circadian regulation of lipid metabolism in ...

PUBLIC LIBRARY SCIENCE2022

The role of nicotinamide riboside metabolism in pancreatic beta cells

Angélique Satoko Cercillieux

Pancreatic beta cells play a major role in the regulation of glucose homeostasis by secreting insulin in response to elevated blood glucose levels. A gradual deterioration of functional beta cell mass and the chronic elevation of blood glucose levels are c ...

EPFL2022

Lipid biosynthesis enzyme Agpat5 in AgRP-neurons is required for insulin-induced hypoglycemia sensing and glucagon secretion

Maxime Jan

The counterregulatory response to hypoglycemia that restores normal blood glucose levels is an essential physiological function. It is initiated, in large part, by incompletely characterized brain hypoglycemia sensing neurons that trigger the secretion of ...

Nature Research2022

Cognitive Impairment and Metabolite Profile Alterations in the Hippocampus and Cortex of Male and Female Mice Exposed to a Fat and Sugar-Rich Diet are Normalized by Diet Reversal

João Miguel das Neves Duarte, Adélaïde Alice Mohr

Diabetes impacts on brain metabolism, structure, and function. Alterations in brain metabolism have been observed in obesity and diabetes models induced by exposure to diets rich in saturated fat and/or sugar and have been linked to memory impairment. Howe ...

INT SOC AGING & DISEASE2022

Islet Encapsulation: New Developments for the Treatment of Type 1 Diabetes

Sandrine Gerber, Léo Bühler, Qixing Zhang, Yi Wang

Islet transplantation is a promising approach for the treatment of type 1 diabetes (T1D). Currently, clinical islet transplantation is limited by allo - and autoimmunity that may cause partial or complete loss of islet function within a short period of tim ...

2022

Machine learning-derived gut microbiome signature predicts fatty liver disease in the presence of insulin resistance

Johan Auwerx, Dongryeol Ryu

A simple predictive biomarker for fatty liver disease is required for individuals with insulin resistance. Here, we developed a supervised machine learning-based classifier for fatty liver disease using fecal 16S rDNA sequencing data. Based on the Kangbuk ...

Nature Portfolio2022

Hypothalamic pregnenolone mediates recognition memory in the context of metabolic disorders

Maria del Carmen Sandi Perez, Ioannis Zalachoras, Sara Ramirez Flores

Obesity and type 2 diabetes are associated with cognitive dysfunction. Because the hypothalamus is implicated in energy balance control and memory disorders, we hypothesized that specific neurons in this brain region are at the interface of metabolism and ...

Cell Press2022

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

Sandrine Gerber, Léo Bühler, 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

Investigation of physiological roles of AMPK-activated protein kinase y3

Philipp Jurijvic Rhein

Clinical trials have shown that direct activators of an evolutionary-conserved metabolic sensor, AMP-activated protein kinase (AMPK), are beneficial in preventing/treating a range of metabolic disorders, including type 2 diabetes. These activators, includi ...

EPFL2021

Pancreatic Sirtuin 3 Deficiency Promotes Hepatic Steatosis by Enhancing 5-Hydroxytryptamine Synthesis in Mice With Diet-Induced Obesity

Kristina Schoonjans, Johan Auwerx

Sirtuin 3 (SIRT3) is a protein deacetylase regulating beta-cell function through inhibiting oxidative stress in obese and diabetic mice, but the detailed mechanism and potential effect of beta-cell-specific SIRT3 on metabolic homeostasis, and its potential ...

AMER DIABETES ASSOC2021

Differential roles of GDF15 and FGF21 in systemic metabolic adaptation to the mitochondrial integrated stress response

Johan Auwerx, Jun Yong Kim

Perturbation of mitochondrial proteostasis provokes cell autonomous and cell non-autonomous responses that contribute to homeostatic adaptation. Here, we demonstrate distinct metabolic effects of hepatic metabokines as cell non-autonomous factors in mice w ...

CELL PRESS2021

SMN Depleted Mice Offer a Robust and Rapid Onset Model of Nonalcoholic Fatty Liver Disease

Bernard Schneider

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is considered a health epidemic with potential devastating effects on the patients and the healthcare systems. Current preclinical models of NAFLD are invariably imperfect and generally take a lon ...

2021

Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965

Kei Sakamoto, Katyayanee Neopane

SBI-0206965, originally identified as an inhibitor of the autophagy initiator kinase ULK1, has recently been reported as a more potent and selective AMP-activated protein kinase (AMPK) inhibitor relative to the widely used, but promiscuous inhibitor Compou ...

2021

Magnitude of gluconeogenesis and endogenous glucose production: are they predictable in clinical settings?

Marc Anthony David Habisreutinger

Introduction: Regulation of endogenous glucose production (EGP) is essential for glucose homeostasis. It includes gluconeogenesis (GNG) from non-carbohydrate substrates and hepatic glycogenolysis. Both these pathways are dysregulated in acute stress, but t ...

2021

Maternal glucose homeostasis is impaired in mouse models of gestational cholestasis

Kristina Schoonjans

Women with intrahepatic cholestasis of pregnancy (ICP), a disorder characterised by raised serum bile acids, are at increased risk of developing gestational diabetes mellitus and have impaired glucose tolerance whilst cholestatic. FXR and TGR5 are modulato ...

Nature Research2020

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

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

In pancreatic islets from type 2 diabetes patients, the dampened circadian oscillators lead to reduced insulin and glucagon exocytosis

Daniel Sage

Circadian clocks operative in pancreatic islets participate in the regulation of insulin secretion in humans and, if compromised, in the development of type 2 diabetes (T2D) in rodents. Here we demonstrate that human islet alpha- and beta-cells that bear a ...

National Academy of Sciences2020

Targeting Mitochondrial Calcium Uptake with the Natural Flavonol Kaempferol, to Promote Metabolism/Secretion Coupling in Pancreatic beta-cells

Guillaume Jacot, Umberto De Marchi

Pancreatic beta-cells secrete insulin to lower blood glucose, following a meal. Maintenance of beta-cell function is essential to preventing type 2 diabetes. In pancreatic beta-cells, mitochondrial matrix calcium is an activating signal for insulin secreti ...

2020