Endocrinology

  • Article
    | Open Access

    A soluble form of insulin receptor in human plasma has been previously reported. Here the authors demonstrate that insulin receptor is cleaved by BACE1 that can regulate biological active insulin receptor levels in a glucose concentration-dependent manner, both in physiological and diabetic conditions.

    • Paul J. Meakin
    • , Anna Mezzapesa
    •  & Franck Peiretti
  • Article
    | Open Access

    Beige adipocytes can arise from transdifferentiation of mature white adipocytes. Here the authors identify CDK6 as a key molecule involved in the white-to-beige adipocyte transdifferentiation and, therefore, as a regulator of organismal energy homeostasis in mice.

    • Xiaoli Hou
    • , Yongzhao Zhang
    •  & Miaofen G. Hu
  • Article
    | Open Access

    Adipocyte hyperplasia is thought to have beneficial metabolic effects in obesity, but definitive evidence is lacking. Here, Shao et al. promote de novo formation of adipocytes in visceral white adipose tissue (WAT) of adult mice through inducible overexpression of Pparg in Pdgfrβ+ preadipocytes and show that this protects from pathological WAT remodeling.

    • Mengle Shao
    • , Lavanya Vishvanath
    •  &  Rana K. Gupta
  • Article
    | Open Access

    FGF21 exerts beneficial metabolic effects on multiple tissues. Here the authors show that the Fgf21 gene is demethylated during the postnatal suckling period, creating an epigenetic memory that determines the responsiveness of the Fgf21 gene to inducers such as PPARα activators or fasting in adulthood.

    • Xunmei Yuan
    • , Kazutaka Tsujimoto
    •  & Yoshihiro Ogawa
  • Article
    | Open Access

    Genome-wide association studies have uncovered several loci associated with diabetes risk. Here, the authors reanalyse public type 2 diabetes GWAS data to fine map 50 known loci and identify seven new ones, including one near ATGR2 on the X-chromosome that doubles the risk of diabetes in men.

    • Sílvia Bonàs-Guarch
    • , Marta Guindo-Martínez
    •  & David Torrents
  • Article
    | Open Access

    FFAR1 receptor is highly expressed in beta cells and its activation has been suggested as therapy against type-2 diabetes. Here, Tunaru et al. show that 20-hydroxyeicosatetraenoic acid, produced within the islets upon glucose stimulation, acts in an autocrine manner to stimulate insulin secretion via FFAR1 activation.

    • Sorin Tunaru
    • , Remy Bonnavion
    •  & Stefan Offermanns
  • Article
    | Open Access

    CCR5 is a co-receptor for HIV, and loss of function is associated with lower incidence of HIV but also with bone-destructive diseases. Here the authors show that ablation of CCR5 impairs osteoclast function and improves resistance to osteoporosis in mouse models.

    • Ji-Won Lee
    • , Akiyoshi Hoshino
    •  & Tadahiro Iimura
  • Article
    | Open Access

    Early life exposure to endocrine disrupting chemicals has been linked to increased adiposity during adulthood. Here Chamorro-García et al. show that ancestral exposure to the obesogen tributyltin causes obesity in untreated F4 generation male descendants by inducing heritable changes in genome architecture that promote a thrifty phenotype.

    • Raquel Chamorro-Garcia
    • , Carlos Diaz-Castillo
    •  & Bruce Blumberg
  • Article
    | Open Access

    Circulating hormones undergo fluctuations during sleep. Here, the authors increase electroencephalographic slow oscillations (SO) during sleep in men using an auditory closed-loop stimulation, and show that the circulating level of cortisol, aldosterone and immune cell count can be altered.

    • Luciana Besedovsky
    • , Hong-Viet V. Ngo
    •  & Jan Born
  • Article
    | Open Access

    Cell-based hormone replacement therapy (cHRT) may be an alternative therapy to pharmacological (p)HRT. Here, the authors show that implanted 3D bioengineered ovarian constructs of granulosa and theca cells in ovariectomized rats recapitulate native cell interactions and improve efficacy compared to similar doses of pHRT.

    • Sivanandane Sittadjody
    • , Justin M. Saul
    •  & Emmanuel C. Opara
  • Article
    | Open Access

    During obesity, chronic inflammation leads to insulin resistance and diabetes. Here, Brenachot et al. show that Protein Tyrosine Phosphatase Receptor Gamma is upregulated in obesity by inflammatory signals and correlates with insulin resistance in humans. Its deletion in mouse models of obesity and inflammation ameliorates insulin resistance by suppressing glucose production.

    • Xavier Brenachot
    • , Giorgio Ramadori
    •  & Roberto Coppari
  • Article
    | Open Access

    Dysregulation of insulin secretion dynamics plays a role in diabetes development. Here, the authors build a mathematical model of hepatic insulin signaling and propose a sequential model of post-meal control of glucose and lipids, according to which delayed aPKC suppression would contribute to selective hepatic insulin resistance.

    • Gang Zhao
    • , Dagmar Wirth
    •  & Michael Meyer-Hermann
  • Article
    | Open Access

    Maturity-onset diabetes of the young (MODY) is the most common subtype of familial diabetes. Here, Patel et al. use targeted DNA sequencing of MODY patients and large-scale publically available data to show that RFX6 heterozygous protein truncating variants cause reduced penetrance MODY.

    • Kashyap A. Patel
    • , Jarno Kettunen
    •  & Michael N. Weedon
  • Article
    | Open Access

    Brown and beige adipose tissues dissipate heat via uncoupling protein 1 (UCP1). Here the authors show that the stress activated kinase MKK6 acts as a repressor of UCP1 expression, suggesting that its inhibition promotes adipose tissue browning and increases organismal energy expenditure.

    • Nuria Matesanz
    • , Edgar Bernardo
    •  & Guadalupe Sabio
  • Article
    | Open Access

    Liver mitochondrial metabolism plays an important role for glucose and lipid homeostasis and its alterations contribute to metabolic disorders, including fatty liver and diabetes. Here Perry et al. develop a method for the measurement of hepatic fluxes by using lactate and glucose tracers in combination with NMR spectroscopy.

    • Rachel J. Perry
    • , Liang Peng
    •  & Gerald I. Shulman
  • Article
    | Open Access

    Hepatic gluconeogenesis is tightly regulated at transcriptional level and is essential for survival during prolonged fasting. Here Wang et al. show that the mitochondrial enriched GCN5-like 1 protein controls hepatic glucose production by regulating FoxO1 protein levels via proteasome-dependent degradation and, in turn, gluconeogenic gene expression.

    • Lingdi Wang
    • , Iain Scott
    •  & Michael N. Sack
  • Article
    | Open Access

    The hypothalamic-pituitary-thyroid (HPT) axis regulates a wide range of physiological processes. Here the authors show that hypothalamic tanycytes play a role in the homeostatic regulation of the HPT axis; activation of TRH signaling in tanycytes elevates their intracellular Ca2+ via Gαq/11 pathway, ultimately resulting in reduced TRH release into the pituitary vessels.

    • Helge Müller-Fielitz
    • , Marcus Stahr
    •  & Markus Schwaninger
  • Article
    | Open Access

    Fatty liver is one of the major features of metabolic syndrome and its development is associated with deregulation of systemic lipid and glucose homeostasis. Here Heidenreich et al. show that retinol saturase is implicated in hepatic lipid metabolism by regulating the activity of the transcription factor ChREBP.

    • Steffi Heidenreich
    • , Nicole Witte
    •  & Michael Schupp
  • Article
    | Open Access

    Harmful chemicals that disrupt the endocrine system and hormone regulation have been associated with obesity. Here the authors apply a human pluripotent stem cell-based platform to study the effects of such compounds on developing gut endocrine and neuroendocrine systems.

    • Uthra Rajamani
    • , Andrew R. Gross
    •  & Dhruv Sareen
  • Article
    | Open Access

    Elevated plasma LPS levels have been associated with insulin resistance. Here Cao et al. show that LPS induces ER stress and P300 activity via the XBP1/IRE1 pathway. P300 acetylates IRS1/2 and inhibits its binding with the insulin receptor. The consequent impairment of insulin signaling can be rescued by pharmacological inhibition of P300.

    • Jia Cao
    • , Jinghua Peng
    •  & Ling He
  • Article
    | Open Access

    The influence of insulin on food preference and the corresponding underlying neural circuits are unknown in humans. Here, the authors show that increasing insulin changes food preference by modulating mesolimbic neural circuits, and that this pattern is changed in insulin-resistant individuals.

    • Lena J. Tiedemann
    • , Sebastian M. Schmid
    •  & Stefanie Brassen
  • Article
    | Open Access

    Deregulation of mTORC1 pathway has been associated with several human diseases including diabetes, neurodegeneration and cancer. Here Blandino-Rosanoet al. show that mTORC1 signalling controls insulin secretion and β-cell maintenance by regulation of β-cell proliferation, apoptosis and autophagy and insulin processing.

    • Manuel Blandino-Rosano
    • , Rebecca Barbaresso
    •  & Ernesto Bernal-Mizrachi
  • Article
    | Open Access

    mTORC1 regulates beta cell survival, function and adaptation to physiologic and pathological stimuli. Here Niet al. demonstrate that that deficiency of Raptor, a component of mTORC1 complex, impairs insulin secretion and glucose tolerance in mice by affecting maturation of beta cells during the postnatal period.

    • Qicheng Ni
    • , Yanyun Gu
    •  & Qidi Wang
  • Article
    | Open Access

    Type 2 diabetes (T2D) is a heterogeneous disorder characterized by insulin resistance and impaired insulin secretion. Here Axelssonet al. show that Sox5, which is reduced in diabetes, regulates a set of differentially expressed genes in T2D and its genetic and pharmacological induction improves insulin secretion by diabetic islets.

    • A. S. Axelsson
    • , T. Mahdi
    •  & A. H. Rosengren
  • Article
    | Open Access

    Bone loss is common in patients with diabetes, but the underlying molecular and cellular mechanisms are unclear. Here the authors show high succinate levels in mice with type 2 diabetes and that succinate can signal through succinate receptor 1 on osteoclasts to induce bone resorption.

    • Yuqi Guo
    • , Chengzhi Xie
    •  & Xin Li
  • Article
    | Open Access

    Lipid turnover in tissues can be calculated from ratios of different carbon isotopes. Here the authors use this approach to study lipid turnover in two distinct adipose tissue depots and find that, in obese individuals, visceral fat is more lipolytic than subcutaneous fat.

    • Kirsty L. Spalding
    • , Samuel Bernard
    •  & Peter Arner
  • Article
    | Open Access

    Long-term consumption of a calorie-rich diet persistently activates brain microglia. Here, the authors show that microglial activity in mouse brains oscillates daily in conjunction with feeding, and that TNFα, secreted by activated microglia, induces mitochondrial stress in satiety-promoting POMC neurons.

    • Chun-Xia Yi
    • , Marc Walter
    •  & Matthias H. Tschöp
  • Article
    | Open Access

    p53 regulates lipid metabolism and fatty acid oxidation, and its inactivation promotes diet-induced liver steatosis. Here Porteiroet al. show that p53 deficiency leads to compensatory p63 upregulation, which, in turn, triggers endoplasmic reticulum stress through IKKβ activation, fatty acid synthesis and lipid accumulation.

    • Begoña Porteiro
    • , Marcos F. Fondevila
    •  & Ruben Nogueiras
  • Article
    | Open Access

    Steviol glycosides are sweet-tasting compounds isolated from a South American shrub and are increasingly used as sweeteners in foods and beverages. Philippaertet al. demonstrate that steviol glycosides potentiate Ca2+-dependent TRPM5 activity and promote glucose-induced insulin secretion and glucose tolerance.

    • Koenraad Philippaert
    • , Andy Pironet
    •  & Rudi Vennekens
  • Article
    | Open Access

    Bisphenol A is used in the production of many plastic products, but has adverse health effects and is therefore being replaced. Here the authors show that its substitute, fluorene-9-bisphenol, is released from commercial plastic bottles into drinking water, and has anti-oestrogenic effects in mice.

    • Zhaobin Zhang
    • , Ying Hu
    •  & Jianying Hu
  • Article
    | Open Access

    The kinase FAK is important for integrin signalling and promotes cell survival. Here, the authors demonstrate FAK regulates adipocyte survival, and is particularly important for maintaining insulin sensitivity during adipose tissue expansion in the context of a calorie-rich diet.

    • Cynthia T. Luk
    • , Sally Yu Shi
    •  & Minna Woo
  • Article
    | Open Access

    Feeding control requires the integration and coordination of motivational, sensory and motor circuits in the brain. Here, the authors discover a set of neurons that regulate feeding inDrosophilaby promoting insulin release, and whose activity reflects physiological hunger and satiety states of flies.

    • Yin Peng Zhan
    • , Li Liu
    •  & Yan Zhu
  • Article
    | Open Access

    GCN5 inhibits hepatic gluconeogenesis through acetylation of PGC-1α. Here the authors show that GCN5 also activates hepatic gluconeogenesis by acetylating histone H3K9, and that the affinity of GCN5 for its different substrates is regulated via phosphorylation at S275 by PKA in a CITED2-dependent manner.

    • Mashito Sakai
    • , Tomoko Tujimura-Hayakawa
    •  & Michihiro Matsumoto
  • Article
    | Open Access

    TSC22D4 regulates hepatic lipoprotein production, but has so far mainly been studied in the context of cancer cachexia. Here, the authors show TSC22D4 inhibition improves insulin sensitivity in several mouse models of diabetes, which they attribute at least in part to the induction of secreted LCN13.

    • Bilgen Ekim Üstünel
    • , Kilian Friedrich
    •  & Stephan Herzig
  • Article
    | Open Access

    Parathyroid hormone (PTH) is an endogenous hormone and osteoporosis therapeutic that suppresses sclerostin activity. Here the authors develop SIK inhibitors as potential therapeutic tools and use them to show that PTH-cAMP signalling in osteocytes inhibits SIK2 from driving Hdac4/5 nuclear shuttling to suppress sclerostin.

    • Marc N. Wein
    • , Yanke Liang
    •  & Henry M. Kronenberg
  • Article
    | Open Access

    The TOR and insulin/IGF signalling (IIS) network are central responses to wound healing. Here the authors develop a technique of live imaging of laser-induced epidermal wounds to flies and show that TOR and IIS are independently required for wound healing, which may have implications for diabetic wound healing and its treatment.

    • Parisa Kakanj
    • , Bernard Moussian
    •  & Maria Leptin
  • Article
    | Open Access

    Type 1 diabetes is driven by T-cell autoimmunity to pancreatic islet cells. Here the authors show that autoreactive anti-IL-2 T and B cells are present in type 1 diabetes patients, and that anti-IL-2 antibodies precede diabetes onset in mice, suggesting their potential as a diagnostic marker.

    • Louis Pérol
    • , John M. Lindner
    •  & Eliane Piaggio
  • Article
    | Open Access

    Hypothalamic melanocortin-4-receptors (MC4R) regulate food preference in rodents, but their role in humans is unclear. Here, the authors perform food preference and liking tests in humans with MC4R mutations and find that they prefer fatty food more, but sweet food less, than people without MC4R mutations.

    • Agatha A. van der Klaauw
    • , Julia M. Keogh
    •  & I. Sadaf Farooqi
  • Article
    | Open Access

    GDF11 is related to myostatin yet has no known role in postnatal bone turnover. Here the authors show that recombinant GDF11 injection causes bone loss and impairs healing by driving osteoclastogenesis while inhibiting osteoblast differentiation, plus they show that anti-GDF11 Ab can inhibit bone loss in ovariectomy and ageing mouse models.

    • Weiqing Liu
    • , Liyan Zhou
    •  & Quan Yuan
  • Article
    | Open Access

    Dysfunction or loss of insulin-secreting β cells in the pancreas is a hallmark of diabetes. Here, Dorrell et al.identify four subpopulations of β cells in humans, which differ in gene expression and insulin secretion kinetics, and the abundance of which is altered in patients with type 2 diabetes.

    • Craig Dorrell
    • , Jonathan Schug
    •  & Markus Grompe