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GLP-1 is an incretin hormone and neuromodulator produced by gut enterocytes and CNS neurons. Brierley et al. find that GLP-1 from peripheral and central sources acts independently through distinct gut–brain circuits to suppress eating.

Biglari et al. reveal subgroups of arcuate nucleus hypothalamic neurons that exhibit distinct molecular signatures and feeding-regulatory functions, thus uncovering new regulatory principles in body weight control.

A large-scale multi-omics analysis reports oncogenic alterations that drive medulloblastoma progression, rather than initiation, and the findings show how single-cell technologies can be used for early detection and diagnosis of medulloblastoma.

A series of fluorescent probes is designed that act as dual agonists on both GLP1 and GIP receptors, and are used to image receptor binding activities in tissues and animals.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Glucagon-like peptide 1 (GLP-1) is released from intestinal L-cells following nutrient uptake and enhances insulin release as well as promotes satiety. Here, the authors demonstrate that GLP-1 secreting cells release ATP and that this stimulates nodose neurons and enterocytes in a paracrine manner in vitro.

A large-scale genome-wide meta-analysis conducted across different platforms identifies genetic loci regulating levels of circulating metabolites.

The regulation of energy homeostasis by centrally-produced GLP-1 is not yet fully understood. Here, authors show that GLP-1 neuronal circuitry in the olfactory bulb reduces food intake and enhances insulin secretion in obese mice. The increase in insulin secretion is mediated by a GABA-dependent relay in the paraventricular hypothalamus and decreased sympathetic nerve activity.

A. Kemal Topaloglu and colleagues report the identification of mutations in the neurokinin B receptor and its ligand in families with severe congenital gonadotropin deficiency and pubertal failure. These findings indicate that neurokinin B is a central regulator of human gonadal function.

Impaired glucagon secretion in patients with diabetes causes hypoglycemia. Here the authors show that therapeutic concentrations of insulin inhibit alpha-cell glucagon secretion by stimulating delta-cell insulin receptor and the release of somatostatin. Blocking somatostatin secretion or action ameliorates this effect.

Bile acids exert metabolic effects by modulating FXR receptor activity. Here, Trabelsi et al.show that FXR negatively regulates production of the incretin GLP-1 in enteroendocrine L-cells by reducing glycolysis and that inhibition of FXR improves glucose metabolism by increasing GLP-1 in obese mice.

Glucagon-like peptide-1 receptor is an important regulator of appetite and glucose homeostasis. Here the authors describe super-resolution microscopy and in vivo imaging compatible fluorescent probes, which reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics in islets and brain.

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.

Gribble and Reimann provide a concise overview of the core physiology of GLP-1 secretion and action, and the roles of GLP-1 in human health, disease and therapy.

Helga Ellingsgaard et al. show that secretion of interleukin-6 by muscle in response to exercise, or injection of recombinant protein, increases the expression of the incretin GLP-1 by both intestinal cells and by pancreatic alpha cells, thus potentiating insulin release and improving glycemic control. These results identify a new endocrine loop linking energy demands to homeostatic control while also suggesting further targets for type 2 diabetes therapy.

In patients with diabetes, insulin release from pancreatic β-cells is reduced due to altered islet structure and function. Here, Brereton et al. show that elevated blood glucose underlies these changes and is sufficient to reversibly alter β-cell identity in a mouse model of β-cell dysfunction.

Thirst is regulated by hierarchical neural circuits in the lamina terminalis, and these integrate the instinctive need for water with consequent drinking behaviour to maintain internal water homeostasis.

Somatostatin is secreted by delta cells and inhibits insulin and glucagon secretion. Here Vergari et al. demonstrate a mechanism for somatostatin secretion that is dependent on decreased extracellular potassium and increased intracellular sodium levels, and is altered in islets from patients with diabetes.

An in vitro system that generates three-dimensional cultures of extraembryonic fetal trophoblast cells that differentiate into the two main types of trophoblast can be used to study human placental development.

Argon and luminescence dating of fossil shell infills from Trinil in Java, where Homo erectus lived, reveals that the hominin-bearing deposits are younger than previously thought; perforated shells, a shell tool and an engraved shell indicate that Homo erectus ate freshwater mussels, used their shells as tools and was able to create abstract engravings.

An investigation of the influence of age on the generation of insulin-producing cells after β-cell loss in mice reveals that, whereas α-cells can reprogram to produce insulin from puberty to adulthood, efficient reconstitution in the very young is through δ-cell reprogramming, leading to complete diabetes recovery.

Beumer et al. show that intestinal enteroendocrine cells adjust their hormonal profile during migration from the crypt to the villus, depending on region-specific BMP signalling.

Geoffrey Woods, Jan Senderek and colleagues show that biallelic mutations in PRDM12 cause congenital insensitivity to pain. They further show that PRDM12 is expressed in nociceptors and their progenitors and participates in sensory neuron development in Xenopus.

Veprik et al. show that Acetyl-CoA-carboxylase 1 (ACC1), an enzyme that couples glucose metabolism to lipogenesis, is involved in glucagon secretion and regulates S-acylation of critical glucose-sensing proteins. Loss of ACC1 in pancreatic alpha-cells negatively affects both size and number, as well as glucagon content, while in gut enteroendocrine cells leads to reduced release of glucagon-like peptide 1.

Hormones released in the gut orchestrate pivotal physiological processes. In this Review, the authors present an overview of gut hormones that are involved in the regulation of metabolism, and discuss their action in the gastrointestinal system and beyond.

The gut secretes approximately 20 active hormones with overlapping targets and actions. This Review focuses on the molecular mechanisms underlying the modulation of gut hormone release by food ingestion, obesity and the gut microbiota.

Napso et al. identify proteins from mouse placental endocrine cells and create a comprehensive secretome map of the placenta. The authors compare this secretome map with human placental datasets from women with pregnancy complications and demonstrate the utility of this method in identifying placental protein candidates and transcription factors that could be useful as biomarkers for pregnancy complications.