Abstract:
:Glucagon is released from pancreatic α-cells to activate pathways that raise blood glucose. Its secretion is regulated by α-cell-intrinsic glucose sensing and paracrine control through insulin and somatostatin. To understand the inadequately high glucagon levels that contribute to hyperglycemia in type-2 diabetes (T2D), we analyzed granule behavior, exocytosis and membrane excitability in α-cells of 68 non-diabetic and 21 T2D human donors. We report that exocytosis is moderately reduced in α-cells of T2D donors, without changes in voltage-dependent ion currents or granule trafficking. Dispersed α-cells have a non-physiological V-shaped dose response to glucose, with maximal exocytosis at hyperglycemia. Within intact islets, hyperglycemia instead inhibits α-cell exocytosis, but not in T2D or when paracrine inhibition by insulin or somatostatin is blocked. Surface expression of somatostatin-receptor-2 is reduced in T2D, suggesting a mechanism for the observed somatostatin resistance. Thus, elevated glucagon in human T2D may reflect α-cell insensitivity to paracrine inhibition at hyperglycemia.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Omar-Hmeadi M,Lund PE,Gandasi NR,Tengholm A,Barg Sdoi
10.1038/s41467-020-15717-8subject
Has Abstractpub_date
2020-04-20 00:00:00pages
1896issue
1issn
2041-1723pii
10.1038/s41467-020-15717-8journal_volume
11pub_type
杂志文章abstract::Simultaneous deep brain stimulation (DBS) and functional magnetic resonance imaging (fMRI) constitutes a powerful tool for elucidating brain functional connectivity, and exploring neuromodulatory mechanisms of DBS therapies. Previous DBS-fMRI studies could not provide full activation pattern maps due to poor MRI compa...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-15570-9
更新日期:2020-04-14 00:00:00
abstract::Photosynthesis is nature's route to convert intermittent solar irradiation into storable energy, while its use for an industrial energy supply is impaired by low efficiency. Artificial photosynthesis provides a promising alternative for efficient robust carbon-neutral renewable energy generation. The approach of direc...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9286
更新日期:2015-09-15 00:00:00
abstract::Human mesenchymal stromal cells (hMSCs) are a promising source for engineered cell-based therapies in which genetic engineering could enhance therapeutic efficacy and install novel cellular functions. Here, we describe an optimized Cas9-AAV6-based genome editing tool platform for site-specific mutagenesis and integrat...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16065-3
更新日期:2020-05-18 00:00:00
abstract::Colorectal cancer (CRC) transcriptional subtypes have been recently identified by gene expression profiling. Here we describe an analytical pipeline, microRNA master regulator analysis (MMRA), developed to search for microRNAs potentially driving CRC subtypes. Starting from a microRNA-mRNA tumour expression data set, ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9878
更新日期:2015-11-17 00:00:00
abstract::The use of hyperpolarized agents in magnetic resonance, such as (13)C-labelled compounds, enables powerful new imaging and detection modalities that stem from a 10,000-fold boost in signal. A major challenge for the future of the hyperpolarization technique is the inherently short spin-relaxation times, typically <60 ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9459
更新日期:2015-10-09 00:00:00
abstract::Although the pharmacological effects of fibroblast growth factor 21 (FGF21) are well-documented, uncertainty about its role in regulating excessive energy intake remains. Here, we show that FGF21 improves systemic insulin sensitivity by promoting the healthy expansion of subcutaneous adipose tissue (SAT). Serum FGF21 ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-02677-9
更新日期:2018-01-18 00:00:00
abstract::Hypoxia is a main driver of sprouting angiogenesis, but how tip endothelial cells are directed to hypoxic regions remains poorly understood. Here, we show that an endothelial MST1-FOXO1 cascade is essential for directional migration of tip cells towards hypoxic regions. In mice, endothelial-specific deletion of either...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-08773-2
更新日期:2019-02-19 00:00:00
abstract::The analysis of whole-genome sequencing studies is challenging due to the large number of noncoding rare variants, our limited understanding of their functional effects, and the lack of natural units for testing. Here we propose a scan statistic framework, WGScan, to simultaneously detect the existence, and estimate t...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11023-0
更新日期:2019-07-09 00:00:00
abstract::HIV can be partially contained by host immunity and understanding the basis of this may inform vaccine design. The importance of B-cell function in long-term control is poorly understood. One method of investigating this is in vivo cellular depletion. In this study, we take advantage of a unique opportunity to investi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms1100
更新日期:2010-10-19 00:00:00
abstract::Formation of domain walls in ferroelectrics is not energetically favourable in low-dimensional systems. Instead, vortex-type structures are formed that are driven by depolarization fields occurring in such systems. Consequently, polarization vortices have only been experimentally found in systems in which these fields...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms13484
更新日期:2016-11-16 00:00:00
abstract::It has been observed that concentrated solutions of short DNA oligomers develop liquid crystal ordering as the result of a hierarchically structured supramolecular self-assembly. In mixtures of oligomers with various degree of complementarity, liquid crystal microdomains are formed via the selective aggregation of tho...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms7424
更新日期:2015-03-10 00:00:00
abstract::The development of stimulus-responsive polymeric materials is of great importance, especially for the development of remotely manipulated materials not in direct contact with an actuator. Here we design a photoresponsive supramolecular actuator by integrating host-guest interactions and photoswitching ability in a hyd...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2280
更新日期:2012-01-01 00:00:00
abstract::Break-induced replication (BIR) is a DNA double-strand break repair pathway that leads to genomic instabilities similar to those observed in cancer. BIR proceeds by a migrating bubble where asynchrony between leading and lagging strand synthesis leads to accumulation of long single-stranded DNA (ssDNA). It remains unk...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-01987-2
更新日期:2017-11-27 00:00:00
abstract::With damage tolerance rivalling advanced engineering alloys and thermoplastic forming capabilities analogous to conventional plastics, metallic glasses are emerging as a modern engineering material. Here, we take advantage of their unique electrical and rheological properties along with the classic Lorentz force conce...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms10576
更新日期:2016-02-08 00:00:00
abstract::The liquid and glass states of metal-organic frameworks (MOFs) have recently become of interest due to the potential for liquid-phase separations and ion transport, alongside the fundamental nature of the latter as a new, fourth category of melt-quenched glass. Here we show that the MOF liquid state can be blended wit...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-04553-6
更新日期:2018-06-15 00:00:00
abstract::The importance of metabolism in macrophage function has been reported, but the in vivo relevance of the in vitro observations is still unclear. Here we show that macrophage metabolites are defined in a specific tissue context, and these metabolites are crucially linked to tissue-resident macrophage functions. We find ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-02092-0
更新日期:2017-12-12 00:00:00
abstract::Although influenza viruses lead to severe illness in high-risk populations, host genetic factors associated with severe disease are largely unknown. As the HLA-A*68:01 allele can be linked to severe pandemic 2009-H1N1 disease, we investigate a potential impairment of HLA-A*68:01-restricted CD8+ T cells to mount robust...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-13346-4
更新日期:2019-12-06 00:00:00
abstract::The importance of singlet oxygen (1O2) in the environmental and biomedical fields has motivated research for effective 1O2 production. Electrocatalytic processes hold great potential for highly-automated and scalable 1O2 synthesis, but they are energy- and chemical-intensive. Herein, we present a Janus electrocatalyti...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-20071-w
更新日期:2020-12-04 00:00:00
abstract::Angiogenesis is essential for tissue development, wound healing and tissue perfusion, with its dysregulation linked to tumorigenesis, rheumatoid arthritis and heart disease. Here we show that pro-angiogenic stimuli couple to NADPH oxidase-dependent generation of oxidants that catalyse an activating intermolecular-disu...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms8920
更新日期:2015-08-10 00:00:00
abstract::Much of the world's Li deposits occurs as basinal brines in magmatic orogens, particularly in continental volcanic arcs. However, the exact origin of Li enrichment in arc magmatic systems is not clear. Here, we show that, globally, primitive arc magmas have Li contents and Li/Y ratios similar to mid-ocean ridge basalt...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-19106-z
更新日期:2020-10-20 00:00:00
abstract::Gut microbiota has been implicated in major diseases affecting the human population and has also been linked to triglycerides and high-density lipoprotein levels in the circulation. Recent development in metabolomics allows classifying the lipoprotein particles into more details. Here, we examine the impact of gut mic...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-13721-1
更新日期:2019-12-20 00:00:00
abstract::How are memories transferred from short-term to long-term storage? Systems-level memory consolidation is thought to be dependent on the coordinated interplay of cortical slow waves, thalamo-cortical sleep spindles and hippocampal ripple oscillations. However, it is currently unclear how the selective interaction of th...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11444-x
更新日期:2019-08-08 00:00:00
abstract::Acoustic waves, capable of transmitting through optically opaque objects, have been widely used in biomedical imaging, industrial sensing and particle manipulation. High-fidelity wave front shaping is essential to further improve performance in these applications. An acoustic analog to the successful spatial light mod...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-18347-2
更新日期:2020-09-10 00:00:00
abstract::Urbanisation is an important global driver of biodiversity change, negatively impacting some species groups whilst providing opportunities for others. Yet its impact on ecosystem services is poorly investigated. Here, using a replicated experimental design, we test how Central European cities impact flying insects and...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-14496-6
更新日期:2020-01-29 00:00:00
abstract::In budding yeast, overcoming of a critical size to enter S phase and the mitosis/mating switch--two central cell fate events--take place in the G1 phase of the cell cycle. Here we present a mathematical model of the basic molecular mechanism controlling the G1/S transition, whose major regulatory feature is multisite ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11372
更新日期:2016-04-20 00:00:00
abstract::Seeded propagation of amyloid-beta (Aβ) pathology is suggested to contribute to the progression of Alzheimer's disease. Local overproduction of aggregation-prone Aβ variants could explain the focal initiation of a seeding cascade that subsequently triggers widespread pathology. Several animal models support this seedi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-00579-4
更新日期:2017-09-11 00:00:00
abstract::Aberrant metabolism of cancer cells is well appreciated, but the identification of cancer subsets with specific metabolic vulnerabilities remains challenging. We conducted a chemical biology screen and identified a subset of neuroendocrine tumors displaying a striking pattern of sensitivity to inhibition of the choles...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07959-4
更新日期:2019-01-09 00:00:00
abstract::Primitive carbonaceous chondrites contain a large array of organic compounds dominated by insoluble organic matter (IOM). A striking feature of this IOM is the systematic enrichment in deuterium compared with the solar hydrogen reservoir. This enrichment has been taken as a sign of low-temperature ion-molecule or gas-...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9567
更新日期:2015-10-13 00:00:00
abstract::Integrating epigenetic data with genome-wide association study (GWAS) results can reveal disease mechanisms. The genome sequence itself also shapes the epigenome, with CpG density and transcription factor binding sites (TFBSs) strongly encoding the DNA methylome. Therefore, genetic polymorphism impacts on the observed...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-01586-1
更新日期:2018-01-02 00:00:00
abstract::Myelinating oligodendrocytes enable fast propagation of action potentials along the ensheathed axons. In addition, oligodendrocytes play diverse non-canonical roles including axonal metabolic support and activity-dependent myelination. An open question remains whether myelination also contributes to information proces...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-19152-7
更新日期:2020-10-30 00:00:00