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KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response

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Statistical learning quantifies transposable element-mediated cis-regulation

Didier Trono, Evaristo Jose Planet Letschert, Julien Léonard Duc, Alexandre Coudray, Julien Paul André Pontis, Delphine Yvette L Grun, Cyril David Son-Tuyên Pulver, Shaoline Sheppard

Background: Transposable elements (TEs) have colonized the genomes of most metazoans, and many TE-embedded sequences function as cis-regulatory elements (CREs) for genes involved in a wide range of biological processes from early embryo- genesis to innate ...

2023

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

Jonathan Paz Montoya, Howard Riezman

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

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

Sandrine Gerber, Luca Szabó, Léo Bühler

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

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 ...

NATL ACAD SCIENCES2020

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

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Aims/hypothesis In islets from individuals with type 2 diabetes and in islets exposed to chronic elevated glucose, mitochondrial energy metabolism is impaired. Here, we studied early metabolic changes and mitochondrial adaptations in human beta cells durin ...

2020

Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors that are characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with ...

2020

L-Cell Differentiation Is Induced by Bile Acids Through GPBAR1 and Paracrine GLP-1 and Serotonin Signaling

Kristina Schoonjans, Giovanni Sorrentino

Glucagon-like peptide 1 (GLP-1) mimetics are effective drugs for treatment of type 2 diabetes, and there is consequently extensive interest in increasing endogenous GLP-1 secretion and L-cell abundance. Here we identify G-protein-coupled bile acid receptor ...

AMER DIABETES ASSOC2020

Glucose sensing and regulation of insulin secretion are the two main functions performed by the pancreatic beta-cell. Together these processes contribute to the tight control of blood glucose in our body. Compromising the ability of the beta-cells to prope ...

EPFL2019

Chromatin three-dimensional interactions mediate genetic effects on gene expression

David Hacker, Giovanna Ambrosini, Philipp Bucher, Sanjeev Kumar

Studying the genetic basis of gene expression and chromatin organization is key to characterizing the effect of genetic variability on the function and structure of the human genome. Here we unravel how genetic variation perturbs gene regulation using a da ...

2019