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Augmented mitochondrial energy metabolism is an early response to chronic glucose stress in human pancreatic beta cells

Loïc Dayon, Andreas Wiederkehr, Sofia Moco, Isabelle Chareyron

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

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

Patient respiratory-triggered quantitative T-2 mapping in the pancreas

Tobias Kober, Tom Hilbert, Reto Meuli, Josefina Adriana Maria Bastiaansen

Background Long acquisition times and motion sensitivity limit T-2 mapping in the abdomen. Accelerated mapping at 3 T may allow for quantitative assessment of diffuse pancreatic disease in patients during free-breathing. Purpose To test the feasibility of ...

2019

Aberrant Accumulation of the Diabetes Autoantigen GAD65 in Golgi Membranes in Conditions of ER Stress and Autoimmunity

Jeffrey Alan Hubbell, Steinunn Baekkeskov Hanahan, Chiara Cianciaruso, Miriella Carmela Pasquier, Edward Allen Phelps

Pancreatic islet β-cells are particularly susceptible to endoplasmic reticulum (ER) stress, which is implicated in β-cell dysfunction and loss during the pathogenesis of type 1 diabetes (T1D). The peripheral membrane protein GAD65 is an autoantigen in huma ...

Amer Diabetes Assoc2016

Pancreatic islet cells isolation and transplantation into the bone marrow

Sandrine Gerber

Bone marrow is currently being considered as an alternative site for pancreatic islet transplantation. The goal of the present review is to report preclinical and clinical studies taking advantage of this new implantation site. Preclinical studies in mice ...

2016

REST represses a subset of the pancreatic endocrine differentiation program

Anne Grapin-Botton, Yung Hae Kim

To contribute to devise successful beta-cell differentiation strategies for the cure of Type 1 diabetes we sought to uncover barriers that restrict endocrine fate acquisition by studying the role of the transcriptional repressor REST in the developing panc ...

Academic Press Inc Elsevier Science2015

Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis

Laurence Anne E Lemaire

Mutations in Bicaudal C1 (BICC1), an RNA binding protein involved in translational regulation, have been associated with cystic kidney disease both in humans and in mice. Since kidney cysts associate with pancreatic defects in several human syndromes, we i ...

EPFL2015

Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis

Daniel Constam, Anne Grapin-Botton, Jacques Rougemont, Joan Goulley, Yung Hae Kim, Laurence Anne E Lemaire

In human, mutations in bicaudal C1 (BICC1), an RNA binding protein, have been identified in patients with kidney dysplasia. Deletion of Bicc1 in mouse leads to left-right asymmetry randomization and renal cysts. Here, we show that BICC1 is also expressed i ...

Company Of Biologists Ltd2015

Compartmentalization of GABA synthesis by GAD67 differs between pancreatic beta cells and neurons

Steinunn Baekkeskov Hanahan, Chiara Cianciaruso, Miriella Carmela Pasquier, Edward Allen Phelps

The inhibitory neurotransmitter GABA is synthesized by the enzyme glutamic acid decarboxylase (GAD) in neurons and in pancreatic β-cells in islets of Langerhans where it functions as a paracrine and autocrine signaling molecule regulating the function of i ...

Public Library of Science2015

Concise Reviews: In Vitro-Produced Pancreas Organogenesis Models in Three Dimensions: Self-Organization From Few Stem Cells or Progenitors

Filippo De Franceschi, Anne Grapin-Botton, Chiara Greggio

Three-dimensional models of organ biogenesis have recently flourished. They promote a balance between stem/progenitor cell expansion and differentiation without the constraints of flat tissue culture vessels, allowing for autonomous self-organization of ce ...