Publications de Steinunn Baekkeskov Hanahan

Mechanism and effects of pulsatile GABA secretion from cytosolic pools in the human beta cell

Steinunn Baekkeskov Hanahan, Edward Allen Phelps, Petra Catalina Schwalie, Chiara Cianciaruso

Pancreatic beta cells synthesize and secrete the neurotransmitter GABA (gamma-aminobutyric acid) as a paracrine and autocrine signal to help regulate hormone secretion and islet homeostasis. Islet GABA release has classically been described as a secretory- ...

2019

Advances in pancreatic islet monolayer culture on glass surfaces enable super-resolution microscopy and insights into beta cell ciliogenesis and proliferation

Jeffrey Alan Hubbell, Olivier Burri, Miriella Carmela Pasquier, Andreas Wiederkehr, Steinunn Baekkeskov Hanahan, Edward Allen Phelps, Gabriele Galliverti, Chiara Cianciaruso

A robust and reproducible method for culturing monolayers of adherent and well-spread primary islet cells on glass coverslips is required for detailed imaging studies by super-resolution and livecell microscopy. Guided by an observation that dispersed isle ...

Springer Nature2017

Bioengineering strategies for inducing tolerance in autoimmune diabetes

Jeffrey Alan Hubbell, Steinunn Baekkeskov Hanahan, Edward Allen Phelps

Type 1 diabetes is an autoimmune disease marked by the destruction of insulin-producing beta cells in the pancreatic islets. Strategies to delay onset or prevent the autoimmune recognition of beta cell antigens or T cell-mediated killing of beta cells have ...

Elsevier Science Bv2017

Primary human and rat beta cells release the intracellular autoantigens GAD65, IA-2 and proinsulin in exosomes together with cytokine-induced enhancers of immunity

Jeffrey Alan Hubbell, Melody Swartz, Miriella Carmela Pasquier, Davide Demurtas, Sachiko Hirosue, Romain Hamelin, Steinunn Baekkeskov Hanahan, Michele De Palma, Edward Allen Phelps, Chiara Cianciaruso

The target autoantigens in several organ-specific autoimmune diseases, including type 1 diabetes (T1D), are intracellular membrane proteins, whose initial encounter with the immune system is poorly understood. Here we propose a new model for how these prot ...

American Diabetes Association2017

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

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

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

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

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

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

Two distinct mechanisms target GAD67 to vesicular pathways and presynaptic clusters

Steinunn Baekkeskov Hanahan

T he inhibitory neurotransmitter gamma-amino butyric acid (GABA) is synthesized by two isoforms of the enzyme glutamic acid decarboxylase (GAD): GAD65 and GAD67. Whereas GAD67 is constitutively active and produces >90% of GABA in the central nervous system ...

Rockefeller University Press2010

Homing of GAD65 specific autoimmunity and development of insulitis requires expression of both DQ8 and human GAD65 in transgenic mice

Steinunn Baekkeskov Hanahan

MHC-class II genes determine susceptibility in human type-1 diabetes. In their context, presentation of target antigen(s) results in autoimmunity and b-cell destruction. An animal model, in which human b-cell autoantigen(s) are presented to effector cells ...

Elsevier2009

A palmitoylation cycle dynamically regulates partitioning of the GABA-synthesizing enzyme GAD65 between ER-Golgi and post-Golgi membranes

Steinunn Baekkeskov Hanahan

GAD65, the smaller isoform of the enzyme glutamic acid decarboxylase, synthesizes GABA for fine-tuning of inhibitory neurotransmission. GAD65 is synthesized as a soluble hydrophilic protein but undergoes a hydrophobic post-translational modification and be ...

Company of Biologists2008

A combination of three distinct trafficking signals mediates axonal targeting and presynaptic clustering of GAD65

Steinunn Baekkeskov Hanahan

the signals involved in axonal trafficking and presynaptic clustering are poorly defined. Here we show that targeting of the -aminobutyric acid–synthesizing enzyme glutamate decarboxylase 65 (GAD65) to presynaptic clusters is mediated by its palmitoylated ...

Rockefeller University Press2002

A non-cleavable mutant of Fas ligand does not prevent neutrophilic destruction of islet transplants

Steinunn Baekkeskov Hanahan

Background. Fas ligand (FasL) mediates apoptosis of susceptible Fas-expressing lymphocytes, and may contribute to the maintenance of peripheral tolerance. In transplantation models, however, artificial expres- sion of FasL on cellular as well as islet tran ...

Lippincott, Williams & Wilkins2000

Epilepsy in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase

Steinunn Baekkeskov Hanahan

γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain, is synthesized by two glutamate decarboxylase isoforms, GAD65 and GAD67. The separate role of the two isoforms is unknown, but differences in saturation with cofactor ...

National Academy of Sciences1997