• Article |

    Cryo-EM structures of human calcium-sensing receptor reveal intrinsic asymmetry in the receptor homodimer upon activation that is stabilized by calcimimetic drugs adopting distinct poses in the two protomers, priming one protomer for G-protein coupling.

    • Yang Gao
    • , Michael J. Robertson
    •  & Georgios Skiniotis
  • Article |

    A role and mechanism of action are identified for INSP3R1 in the stimulation of hepatic gluconeogenesis and mitochondrial oxidation by glucagon, suggesting that INSP3R1 may be a target for ameliorating dysregulation of hepatic glucose metabolism.

    • Rachel J. Perry
    • , Dongyan Zhang
    •  & Gerald I. Shulman
  • Article |

    The cryo-electron microscopy structure of human thyroglobulin reveals that proximity, flexibility and solvent exposure are key characteristics of its hormonogenic tyrosine pairs, and provides a framework for understanding the formation of thyroid hormones.

    • Francesca Coscia
    • , Ajda Taler-Verčič
    •  & Jan Löwe
  • Article |

    In mouse studies, metformin treatment results in increased secretion of growth/differentiation factor 15 (GDF15), which prevents weight gain in response to high-fat diet, and GDF15-independent lowering of circulating blood glucose.

    • Anthony P. Coll
    • , Michael Chen
    •  & Stephen O’Rahilly
  • Review Article |

    A Review of studies into insulin resistance and hepatic gluconeogenesis associated with obesity and type 2 diabetes.

    • Michael Roden
    •  & Gerald I. Shulman
  • Brief Communications Arising |

    • John Collinge
    • , Zane Jaunmuktane
    •  & Sebastian Brandner
  • Letter |

    Neurotensin, a peptide expressed in the enteroendocrine cells of the small intestine that is released upon fat ingestion, is shown to increase fatty acid absorption, with neurotensin-deficient mice being protected from obesity induced by a high-fat diet.

    • Jing Li
    • , Jun Song
    •  & B. Mark Evers
  • Letter |

    Activation of glucose-sensing neurons in the ventromedial hypothalamic nucleus using radio waves or magnetic fields remotely and non-invasively in vivo increases plasma glucose and glucagon, and suppresses plasma insulin; conversely, remote inhibition of glucose-sensing neurons decreased blood glucose and increased plasma insulin.

    • Sarah A. Stanley
    • , Leah Kelly
    •  & Jeffrey M. Friedman
  • Letter |

    The FXR–CREB axis is identified as a key physiological switch that regulates autophagy during feeding/fasting cycles; in the fed state, the nuclear receptor FXR is shown to suppress autophagy in the liver by inhibiting autophagy-associated lipid breakdown triggered under fasting conditions by the transcriptional activator CREB.

    • Sunmi Seok
    • , Ting Fu
    •  & Jongsook Kim Kemper
  • Letter |

    The nuclear receptors FXR and PPARα are shown to regulate autophagy by competing for binding to shared sites in the promoters of autophagic genes; in the fed state FXR suppresses hepatic autophagy, whereas in the fasted state PPARα is activated and reverses the normal suppression of autophagy.

    • Jae Man Lee
    • , Martin Wagner
    •  & David D. Moore
  • Review Article |

    An alternative view of diabetes is presented in which blood glucose homeostasis is achieved via collective actions of two regulatory systems: a brain-centred glucoregulatory system (BCGS), which works together with the pancreatic islets; defects in both systems may be required for diabetes to occur, and interventions targeting both systems may have greater therapeutic potential.

    • Michael W. Schwartz
    • , Randy J. Seeley
    •  & David D’Alessio
  • Letter |

    Reproductive history influences breast cancer risk but the cellular mechanisms are unclear. Here it is shown that ovarian hormones regulate the size of the mammary stem cell pool in mice. The size of this pool increases when progesterone levels increase during the reproductive cycle. Progesterone probably regulates stem cell numbers through a paracrine mechanism involving induction of RANKL and Wnt in luminal cells.

    • Purna A. Joshi
    • , Hartland W. Jackson
    •  & Rama Khokha