Dr. Nikolay Ninov and Luis Fernando Delgadillo Silva

Leader β-cells drive insulin secretion

Latest Research

  • Letter |

    Here the authors report the results of a first-in-human trial with urolithin A in healthy elderly individuals, demonstrating that the compound is well tolerated and bioavailable after oral administration. They also provide clinical data indicating that urolithin A may improve mitochondrial and cellular health in human muscle.

    • Pénélope A. Andreux
    • , William Blanco-Bose
    • , Dongryeol Ryu
    • , Frédéric Burdet
    • , Mark Ibberson
    • , Patrick Aebischer
    • , Johan Auwerx
    • , Anurag Singh
    •  & Chris Rinsch
  • Article |

    Non-alcoholic steatosis is characterized by lipid accumulation within hepatocytes and can progress to NASH. Haas and colleagues demonstrate that livers from people with NASH show a distinct but reversible gene profile from simple steatosis and accumulation of intrahepatic cDC and CD8 T cells.

    • Joel T. Haas
    • , Luisa Vonghia
    • , Denis A. Mogilenko
    • , An Verrijken
    • , Olivier Molendi-Coste
    • , Sébastien Fleury
    • , Audrey Deprince
    • , Artemii Nikitin
    • , Eloïse Woitrain
    • , Lucie Ducrocq-Geoffroy
    • , Samuel Pic
    • , Bruno Derudas
    • , Hélène Dehondt
    • , Céline Gheeraert
    • , Luc Van Gaal
    • , Ann Driessen
    • , Philippe Lefebvre
    • , Bart Staels
    • , Sven Francque
    •  & David Dombrowicz
  • Article |

    In this study, the authors use ATAC-seq and promoter capture Hi-C data from human adipocytes treated with fatty acids to identify gene–environment (G×E) interactions that influence body-mass index in humans. They report 154 genes that respond to saturated fat and discover 38 new G×E variants for body-mass index in data from the UK Biobank.

    • Kristina M. Garske
    • , David Z. Pan
    • , Zong Miao
    • , Yash V. Bhagat
    • , Caroline Comenho
    • , Christopher R. Robles
    • , Jihane N. Benhammou
    • , Marcus Alvarez
    • , Arthur Ko
    • , Chun Jimmie Ye
    • , Joseph R. Pisegna
    • , Karen L. Mohlke
    • , Janet S. Sinsheimer
    • , Markku Laakso
    •  & Päivi Pajukanta
  • Metabolic Messengers |

    The gut hormone FGF19 and its mouse orthologue Fgf15 are important mediators of the metabolic transition between the fasted and fed state. Here, Gadaleta and Moschetta provide a concise overview of the history of FGF15/FGF19, their physiological role and their molecular mechanism of action.

    • Raffaella Maria Gadaleta
    •  & Antonio Moschetta
  • Article |

    Bioproduct synthesis via reductive metabolism occurs with different efficiencies according to the availability of carbons, ATP and reducing agents. To maximize overall product synthesis efficiency, the authors develop a substrate cofeeding strategy, which circumvents catabolite repression and drives synergy in lipid synthesis from CO2 using two microbes.

    • Junyoung O. Park
    • , Nian Liu
    • , Kara M. Holinski
    • , David F. Emerson
    • , Kangjian Qiao
    • , Benjamin M. Woolston
    • , Jingyang Xu
    • , Zbigniew Lazar
    • , M. Ahsanul Islam
    • , Charles Vidoudez
    • , Peter R. Girguis
    •  & Gregory Stephanopoulos
  • Article |

    Pancreatic β-cells are highly connected, and this network is crucial for the pulsatile release of insulin. Here Salem and colleagues demonstrated the existence of leader β-cells that respond first to glucose and are more closely linked to the other β-cells. They also showed that glucose increases β-cell calcium dynamics and connectivity between the leader and non-leader β-cells.

    • Victoria Salem
    • , Luis Delgadillo Silva
    • , Kinga Suba
    • , Eleni Georgiadou
    • , S. Neda Mousavy Gharavy
    • , Nadeem Akhtar
    • , Aldara Martin-Alonso
    • , David C. A. Gaboriau
    • , Stephen M. Rothery
    • , Theodoros Stylianides
    • , Gaelle Carrat
    • , Timothy J. Pullen
    • , Sumeet Pal Singh
    • , David J. Hodson
    • , Isabelle Leclerc
    • , A. M. James Shapiro
    • , Piero Marchetti
    • , Linford J. B. Briant
    • , Walter Distaso
    • , Nikolay Ninov
    •  & Guy A. Rutter

News & Comment

  • Editorial |

    Awareness of non-alcoholic steatohepatitis (NASH) and its symptoms is essential for early detection, and an informed public is also more likely to take action against NASH development.

  • News & Views |

    The entry of remnants of cholesterol-rich lipoproteins, such as low-density lipoprotein (LDL), from the blood stream into the intima of large arteries initiates and then perpetuates atherosclerosis. A study published in Nature sheds new light on this important process by identifying scavenger receptor BI (SR-BI) as a major receptor that mediates LDL delivery across the endothelium into arteries.

    • Xinbo Zhang
    •  & Carlos Fernández-Hernando
  • News & Views |

    Living organisms face the dual challenge of acquiring enough iron to perform biological functions while preventing toxic iron accretion. A study now shows that sensing of iron-catalysed free radicals by a druggable gene-regulatory pathway helps the body avoid iron poisoning.

    • Sandro Altamura
    •  & Bruno Galy
  • News & Views |

    Interorgan communication is emerging as a critical contributor to nutrient and energy homeostasis. A new study has identified a secreted liver factor that stimulates lipid synthesis in white adipose tissue and exacerbates obesity and insulin resistance.

    • Henry Kuang
    •  & Jiandie D. Lin
  • News & Views |

    A common missense variant (I148M) in patatin-like phospholipase domain-containing protein 3 (PNPLA3) was strongly linked to human fatty liver disease in 2008, but the underlying mechanisms have since remained unclear. Compelling data from Yang et al., published in Nature Metabolism, suggest that PNPLA3 binds ABHD5, sequestering it and preventing it from activating ATGL, the major intracellular triglyceride lipase.

    • Stefano Romeo
    •  & David B. Savage
  • News & Views |

    Increasing pancreatic β-cell proliferation in autoimmune type 1 diabetes (T1D) might restore β-cell mass but would be predicted to exacerbate islet inflammation. A study in Nature Metabolism, however, reports that boosting β-cell proliferation in mouse models of T1D is beneficial, preserving the immunological self-tolerance of islets through the induction of regulatory T cells.

    • Mario Galgani
    •  & Giuseppe Matarese