Volume 1 Issue 11, November 2019

Volume 1 Issue 11

GABA pulses regulate insulin secretion

Release of the neurotransmitter GABA from β-cells is known to regulate insulin secretion. Menegaz et al. now show that GABA is released directly from the cytosol in a pulsatile manner via volume regulatory anion channels and is subsequently taken up by the GABA-permissive taurine transporter TauT. Depicted is a pair of human β-cells immunostained for insulin (red) and α-tubulin (blue).

See Menegaz et al.

Image: Edward Phelps, École Polytechnique Fédérale de Lausanne and University of Florida. Cover Design: Allen Beattie

Comment & Opinion

News & Views

  • News & Views |

    Lifespan is increased and ageing is delayed by lifelong dietary restriction. A study in Nature Metabolism shows that these benefits are reduced when dietary restriction is started in old age, owing to the development of an inflexible nutritional memory within white adipose tissue.

    • Stephen J. Simpson
    •  & David G. Le Couteur
  • News & Views |

    A new study by Menegaz et al. in this issue of Nature Metabolism addresses fundamental questions on the acute regulation and role of GABA secretion in pancreatic islets.

    • Guy A. Rutter
  • News & Views |

    A study in Nature Metabolism reveals a hitherto-unknown enzymatic and physiological role of ABHD5, which acts as a protease that couples extracellular cues to the epigenome of cardiomyocytes by cleaving histone deacetylase 4 (HDAC4).

    • Joshua G. Travers
    •  & Timothy A. McKinsey
  • News & Views |

    The mechanism of alcohol-induced changes in the brain is multi-faceted. Acetate, the product of hepatic alcohol metabolism, might contribute to addictive behaviour by regulating gene expression.

    • Alia Ghrayeb
    • , Eyal Gottlieb
    •  & Inbal Mor

Reviews

  • Review Article |

    Generally, most metabolic diseases are not caused by a mutation or defect in a single gene but instead are multi-factorial, resulting from a combination of genetic and environmental factors; thus, studying them requires a holistic approach. Here, Seldin and colleagues review systems genetics approaches, including their resources and advantages, for studying metabolic diseases.

    • Marcus Seldin
    • , Xia Yang
    •  & Aldons J. Lusis
  • Metabolic Messengers |

    Ceramides are bioactive lipids that regulate cellular signalling processes and metabolic pathways, and are implicated in various metabolic diseases. Here, Summers, Chaurasia and Holland provide a concise overview of the history of ceramides and their physiological roles, mechanisms of action and therapeutic potential.

    • Scott A. Summers
    • , Bhagirath Chaurasia
    •  & William L. Holland

Research

  • Article |

    Dietary restriction (DR) late in life does not improve survival and has little benefit in metabolic health in mice. The absence of a DR gene-expression signature in fat tissue suggests that a ‘nutritional memory’ interferes with the benefits of DR.

    • Oliver Hahn
    • , Lisa F. Drews
    • , An Nguyen
    • , Takashi Tatsuta
    • , Lisonia Gkioni
    • , Oliver Hendrich
    • , Qifeng Zhang
    • , Thomas Langer
    • , Scott Pletcher
    • , Michael J. O. Wakelam
    • , Andreas Beyer
    • , Sebastian Grönke
    •  & Linda Partridge
  • Article |

    In addition to having direct anti-cancer effects, the cardiac glycoside ouabain is shown to kill a broad range of senescent cells, thus suggesting that cardiac glycosides represent a novel class of senolytics.

    • Ana Guerrero
    • , Nicolás Herranz
    • , Bin Sun
    • , Verena Wagner
    • , Suchira Gallage
    • , Romain Guiho
    • , Katharina Wolter
    • , Joaquim Pombo
    • , Elaine E. Irvine
    • , Andrew J. Innes
    • , Jodie Birch
    • , Justyna Glegola
    • , Saba Manshaei
    • , Danijela Heide
    • , Gopuraja Dharmalingam
    • , Jule Harbig
    • , Antoni Olona
    • , Jacques Behmoaras
    • , Daniel Dauch
    • , Anthony G. Uren
    • , Lars Zender
    • , Santiago Vernia
    • , Juan Pedro Martínez-Barbera
    • , Mathias Heikenwalder
    • , Dominic J. Withers
    •  & Jesús Gil
  • Article |

    Emerging findings identify important roles for brain lipoprotein receptors in the control of whole-body energy homoeostasis. Here Lee et al. reveal that IDOL-mediated regulation of VLDLR abundance in neurons, but not in peripheral metabolic tissues, regulates food intake and energy expenditure.

    • Stephen D. Lee
    • , Christina Priest
    • , Mikael Bjursell
    • , Jie Gao
    • , Douglas V. Arneson
    • , In Sook Ahn
    • , Graciel Diamante
    • , J. Edward van Veen
    • , Megan G. Massa
    • , Anna C. Calkin
    • , Jason Kim
    • , Harriet Andersén
    • , Prashant Rajbhandari
    • , Michelle Porritt
    • , Alba Carreras
    • , Andrea Ahnmark
    • , Frank Seeliger
    • , Ingela Maxvall
    • , Pernilla Eliasson
    • , Magnus Althage
    • , Peter Åkerblad
    • , Daniel Lindén
    • , Tracy A. Cole
    • , Richard Lee
    • , Helen Boyd
    • , Mohammad Bohlooly-Y
    • , Stephanie M. Correa
    • , Xia Yang
    • , Peter Tontonoz
    •  & Cynthia Hong
  • Article |

    Al Nabhani et al. show how excessive caloric intake during the postnatal period increases the risk of developing intestinal bowel disease during adulthood, owing to increased intestinal permeability, cytokines and hydrogen sulfide production by the microbiota.

    • Ziad Al Nabhani
    • , Sophie Dulauroy
    • , Emelyne Lécuyer
    • , Bernadette Polomack
    • , Pascal Campagne
    • , Marion Berard
    •  & Gérard Eberl
  • Article |

    Pulsatile GABA secretion from human beta cells via the volume regulatory anion channel (VRAC) and subsequent uptake by the GABA-permissive taurine transporter (TauT) is shown to regulate total insulin secretion and pulsatility.

    • Danusa Menegaz
    • , D. Walker Hagan
    • , Joana Almaça
    • , Chiara Cianciaruso
    • , Rayner Rodriguez-Diaz
    • , Judith Molina
    • , Robert M. Dolan
    • , Matthew W. Becker
    • , Petra C. Schwalie
    • , Rita Nano
    • , Fanny Lebreton
    • , Chen Kang
    • , Rajan Sah
    • , Herbert Y. Gaisano
    • , Per-Olof Berggren
    • , Steinunn Baekkeskov
    • , Alejandro Caicedo
    •  & Edward A. Phelps
  • Article |

    Liu et al. describe a molecular network wherein SIRT7 couples light-driven systemic body temperature cues to hepatic oscillators via HSP70 to ensure circadian phase coherence and glucose homeostasis in the liver.

    • Zuojun Liu
    • , Minxian Qian
    • , Xiaolong Tang
    • , Wenjing Hu
    • , Shimin Sun
    • , Guo Li
    • , Shuju Zhang
    • , Fanbiao Meng
    • , Xinyue Cao
    • , Jie Sun
    • , Cheng Xu
    • , Bing Tan
    • , Qiuxiang Pang
    • , Bosheng Zhao
    • , Zimei Wang
    • , Youfei Guan
    • , Xiongzhong Ruan
    •  & Baohua Liu
  • Article |

    Known as a regulator of lipolysis, ABHD5 is found to also act as a serine protease that cleaves HDAC4 in response to catecholaminergic stimulation, thus resulting in the formation of a polypeptide that protects against metabolic-stress-induced heart failure.

    • Zegeye H. Jebessa
    • , Kumar D. Shanmukha
    • , Matthias Dewenter
    • , Lorenz H. Lehmann
    • , Chang Xu
    • , Friederike Schreiter
    • , Dominik Siede
    • , Xue-Min Gong
    • , Barbara C. Worst
    • , Giuseppina Federico
    • , Sven W. Sauer
    • , Tamas Fischer
    • , Lisa Wechselberger
    • , Oliver J. Müller
    • , Samuel Sossalla
    • , Christoph Dieterich
    • , Patrick Most
    • , Herrmann-Josef Gröne
    • , Cedric Moro
    • , Monika Oberer
    • , Guenter Haemmerle
    • , Hugo A. Katus
    • , Jens Tyedmers
    •  & Johannes Backs

Amendments & Corrections