Abstract:
:The incretin hormones, glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), potentiate insulin secretion and are responsible for the majority of insulin secretion that occurs after a meal. They may also, however, have a fundamental role in pancreatic beta cell development and function, independently of their role in potentiating insulin secretion after a meal. This has led to observations that a loss of GIP or GLP-1 action affects normal beta cell function, however each one of the incretin hormones may compensate when the action of the other is lost and therefore the overall impact of the incretin hormones on beta cell function is not known. We therefore utilized a mouse line deficient in both the GLP-1 and GIP receptor genes, the double incretin receptor knockout (DIRKO), to determine the consequences of a lifelong, complete lack of incretin hormone action on beta cell function, in vivo, in intact animals. We found that DIRKO mice displayed impaired glucose tolerance and insulin secretion in response to both oral glucose and mixed meal tolerance tests compared to wild-type mice. Assessment of beta cell function using the hyperglycemic clamp technique revealed an 80% decrease in first phase insulin response in DIRKO mice, but a normal second phase insulin secretion. A similar decline was seen when wild-type mice were given acute intravenous injection of glucose together with the GLP-1 receptor antagonist Ex9-39. Ex vivo assessments of the pancreas revealed significantly fewer islets in the pancreata of DIRKO mice despite no differences in total pancreatic mass. Insulin secretion from isolated islets of DIRKO mice was impaired to a similar extent to that seen during the hyperglycemic clamp. Insulin secretion in wild-type islets was impaired by acute treatment with Ex9-39 to a similar extent as the in vivo intravenous glucose tolerance tests. In conclusion, a loss of the action of both incretin hormones results in direct impairment of beta cell function both in vivo and in vitro in a process that appears to be independent of the intestinally secreted incretin hormones. We therefore conclude that the incretin hormones together significantly impact both beta-cell function and beta-cell development.
journal_name
Peptidesjournal_title
Peptidesauthors
Omar B,Ahlkvist L,Yamada Y,Seino Y,Ahrén Bdoi
10.1016/j.peptides.2016.03.012subject
Has Abstractpub_date
2016-05-01 00:00:00pages
58-65eissn
0196-9781issn
1873-5169pii
S0196-9781(16)30047-Xjournal_volume
79pub_type
杂志文章相关文献
PEPTIDES文献大全abstract::Double-labeling immunofluorescence of guinea pig tracheobronchial lymph nodes revealed complete coincidence of SP and CGRP immunoreactivities in perivascular nerves and axons of the medullary lymphatic tissue. Additional dynorphin A or cholecystokinin immunoreactivity was seen only in some of the medullary fibers. Ult...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/0196-9781(90)90103-c
更新日期:1990-01-01 00:00:00
abstract::To examine the relationship between glutamate receptors and the action of NC-1900 on a step-through passive avoidance (PA) task in mice, MK-801, an NMDA receptor blocker, and (S)-4-carboxyphenylglycine (4CPG), a group I metabotropic receptor antagonist, were administered intraventricularly (i.c.v.) singly or as co-inj...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/j.peptides.2004.12.014
更新日期:2005-05-01 00:00:00
abstract::To investigate the contribution of the N-terminal sequence of h-EGF to its biological activity and the formation of three intramolecular disulfide bonds by oxidative refolding via air oxidation, five derivatives of h-EGF with a single N-terminal amino acid deletion were synthesized by solid-phase synthesis. The homoge...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/0196-9781(94)00181-2
更新日期:1995-01-01 00:00:00
abstract::Brazilian freshwater stingrays, Potamotrygon gr. orbigyni, are relatively common in the middle-western regions of Brazil, where they are considered an important public health threat. In order to identify some of their naturally occurring toxin peptides available in very low amounts, we combine analytical protocols suc...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/j.peptides.2009.08.004
更新日期:2009-12-01 00:00:00
abstract::Five native pyrokinin-like peptides (Neb-PK-1, Neb-PK-2, Neb-PVK-1, [L9]Neb-PVK-2, [I9]Neb-PVK-2) identified in the neuropeptidome of the flesh fly Neobellieria bullata were compared for their quantitative and/or qualitative effects on puparium formation (pupariation). In a standard pupariation bioassay, both Neb-PVK-...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/j.peptides.2005.08.023
更新日期:2006-03-01 00:00:00
abstract::The cell adhesion molecule, N-cadherin plays a pivotal role in many biological and disease processes. Drugs that modulate N-cadherin function should therefore be useful therapeutic agents. We have used phage display technology to identify amino acid sequences capable of binding to N-cadherin. All of these sequences ha...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/j.peptides.2008.06.025
更新日期:2008-11-01 00:00:00
abstract::Enzymatic cleavage of endogenous peptides is a commonly used principle to initiate, modulate and terminate action for instance among cytokines and peptide hormones. The incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and the related hormone glucagon-like pepti...
journal_title:Peptides
pub_type: 杂志文章,评审
doi:10.1016/j.peptides.2019.170224
更新日期:2020-03-01 00:00:00
abstract::In the epileptic brain, hippocampal dentate granule cells become synaptically interconnected through the sprouting of mossy fibers. This new circuitry is expected to facilitate epileptiform discharge. Prolonged seizures induce the long-lasting neoexpression of neuropeptide Y (NPY) in mossy fibers. NPY is released spon...
journal_title:Peptides
pub_type: 杂志文章,评审
doi:10.1016/j.peptides.2006.07.026
更新日期:2007-02-01 00:00:00
abstract::The extractability of neurotensin (NT) from porcine ileal mucosa was studied by comparison of eight extraction procedures. Tissue content of neurotensin-like immunoreactivity was quantitated and characterized by sequence-specific radioimmunoassays and gel filtration chromatography. Homogenization prior to boiling in e...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/0196-9781(87)90038-6
更新日期:1987-07-01 00:00:00
abstract::Obestatin is produced in the stomach from proghrelin by post-translational cleavage. The initial report claimed anorexigenic effects of obestatin in mice. Contrasting studies indicated no effect of obestatin on food intake (FI). We investigated influences of metabolic state (fed/fasted), environmental factors (dark/li...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/j.peptides.2008.01.020
更新日期:2008-06-01 00:00:00
abstract::Antibodies directed against amyloid beta protein (AssP) have been suggested to be effective in the treatment of Alzheimer's disease (AD). Here, we used in vivo and in vitro models to test some of the mechanisms by which antibodies may produce their effects. We found that the blood-to-brain uptake of murine AssP1-42 wa...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/j.peptides.2004.09.016
更新日期:2005-02-01 00:00:00
abstract::The vasoactive peptide urotensin-II (U-II) is best known for its ability to regulate peripheral vascular and cardiac contractile function in vivo, and recent in vitro studies have suggested a role for the peptide in the control of vascular remodeling by inducing smooth muscle proliferation and fibroblast-mediated coll...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/j.peptides.2005.05.028
更新日期:2005-12-01 00:00:00
abstract::There are two distinct mRNAs that encode the precursor to gastrin-releasing peptide (GRP) in rat brain. These two messages arise from separate transcription initiation sites located approximately 400 base pairs apart, which are presumably regulated by separate promoters. In the present study, we mapped the distributio...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/0196-9781(89)90052-1
更新日期:1989-03-01 00:00:00
abstract::Deltorphin, a heptapeptide that selectively binds to delta receptors, was intracerebroventricularly administered to mice belonging to the strains C57BL/6 and DBA/2 immediately after training in a one-trial inhibitory avoidance task. The retention performance of both strains was improved by the peptide administration, ...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/0196-9781(90)90063-b
更新日期:1990-05-01 00:00:00
abstract::Self-administration of ethanol and food share many common features and Richter hypothesized that an increase in ethanol consumption would decrease feeding to balance the excess calories contained in the ethanol. Previously, we have shown that individual alcohol consumption correlates with neurotransmitter gene express...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/j.peptides.2007.09.011
更新日期:2007-12-01 00:00:00
abstract::A comparison of the conformational characteristics of the related hormones [Nle(15)] gastrin-17 and [Tyr(9)-SO(3)] cholecystokinin-15, in membrane-mimetic solutions of dodecylphosphocholine micelles and water, was undertaken using NMR spectroscopy to investigate the possibility of a structural motif responsible for th...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/j.peptides.2007.09.008
更新日期:2007-11-01 00:00:00
abstract::Urotensin II (UII) induces the development of cardiac remodeling and atherosclerosis by promoting hypertrophy of cardiomyocytes and mitogenesis of fibroblasts and vascular smooth muscle cells. But its effect on cardiac side population cells (CSPs), one of somatic stem cells, is unclear. The present study examined the ...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/j.peptides.2011.01.024
更新日期:2011-05-01 00:00:00
abstract::The expression of the relaxin-3 gene, detected as a new member of the insulin superfamily using human genomic databases, is abundantly present in the brain and testis. Intracerebroventricularly (icv) administered relaxin-3 stimulates food intake. Icv administered relaxin (identical to relaxin-2 in humans) affects the ...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/j.peptides.2010.02.020
更新日期:2010-06-01 00:00:00
abstract::A neuropeptide F (NPF) was isolated from the fruit fly, Drosophila mellanogaster, based on a radioimmunoassay for a gut peptide from the corn earworm, Helicoverpa zea. A partial sequence was obtained from the fly peptide, and a genomic sequence coding for NPF was cloned after inverse polymerase chain reaction and show...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/s0196-9781(99)00097-2
更新日期:1999-01-01 00:00:00
abstract::Enzyme-resistant receptor agonists of the incretin hormone glucagon-like peptide-1 (GLP-1) have shown positive therapeutic effects in people with type 2 diabetes mellitus (T2DM). T2DM has detrimental effects on brain function and impairment of cognition and memory formation has been described. One of the underlying me...
journal_title:Peptides
pub_type: 杂志文章,评审
doi:10.1016/j.peptides.2017.11.017
更新日期:2018-02-01 00:00:00
abstract::Urotensin II (U-II) is a vasoactive peptide with many potent effects in the cardiorenovascular system. U-II activates a G-protein-coupled receptor termed UT. UT and U-II are highly expressed in the cardiovascular and renal system. Patients with various cardiovascular diseases show high U-II plasma levels. It was demon...
journal_title:Peptides
pub_type: 杂志文章,评审
doi:10.1016/j.peptides.2007.08.029
更新日期:2008-05-01 00:00:00
abstract::Antimicrobial peptides, molecules produced in many different organisms, have high biocidal activity against several microorganisms. However, several questions about these molecules remain unclear. Therefore, this report details a systematic survey of the literature on the use of antimicrobial peptides against oral pat...
journal_title:Peptides
pub_type: 杂志文章,评审
doi:10.1016/j.peptides.2012.05.015
更新日期:2012-08-01 00:00:00
abstract::Higher plasma copeptin level has been associated with poor outcomes of critical illness. The present study was undertaken to investigate the plasma copeptin concentrations in children with traumatic brain injury (TBI) and to analyze the correlation of copeptin with disease outcome. Plasma copeptin concentrations of 12...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/j.peptides.2013.01.015
更新日期:2013-04-01 00:00:00
abstract::The presence of alpha-hANP immunoreactive material in human heart and plasma was investigated with a specific and sensitive radioimmunoassay and immunohistochemical method. It was found that alpha-hANP immunoreactive staining of specific atrial granules was located around the nucleus of atrial cardiocytes. No immunore...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/0196-9781(86)90057-4
更新日期:1986-01-01 00:00:00
abstract::Heat-stable enterotoxin b (STb) of Escherichia coli is a 48-amino acid basic, disulfide-bonded peptide that causes intestinal secretion in experimental animal models. Recent evidence suggests that the in vivo mechanism of STb action involves release of 5-hydroxytryptamine (5-HT) and production of prostaglandin E2 (PGE...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/0196-9781(96)00033-2
更新日期:1996-01-01 00:00:00
abstract::Intravenous (IV) infusions of neurotensin (NT) in anesthetized guinea pigs elicited dose-dependent pressor effects and tachycardia. Both effects were significantly reduced or abolished in guinea pigs given a chronic treatment with the neurotoxin capsaicin. In guinea pig isolated atria NT evoked a positive inotropic an...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/0196-9781(87)90140-9
更新日期:1987-11-01 00:00:00
abstract::Neuropeptide Y (NPY) receptor binding sites have been characterized in rat brain using both membrane preparations and receptor autoradiography. Radiolabelled NPY binds with high affinity and specificity to an apparent single class of sites in rat brain membrane preparations. The ligand selectivity pattern reveals stro...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/0196-9781(86)90061-6
更新日期:1986-01-01 00:00:00
abstract::Female Sprague-Dawley rat pups were injected SC with either ACTH(1-24) (0.5 mg/kg) or saline vehicle once daily from postnatal day 1 (day of birth) to day 7. Plasma corticosterone (CORT) levels were recorded via radioimmunoassay (RIA) on day 4 to measure adrenal response to these treatments. Hypothalamic 5-HT and DA f...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/0196-9781(93)90056-m
更新日期:1993-03-01 00:00:00
abstract::The beta-casein-derived octapeptide RINKKIEK is a noncompetitive inhibitor of soybean lipoxygenase (LOX). To investigate the molecular determinants for the enzyme-peptide interaction, a peptide library containing substitutional analogs of RINKKIEK was prepared by SPOT synthesis and analyzed for interaction with fluore...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/j.peptides.2007.09.018
更新日期:2007-12-01 00:00:00
abstract::Cholecystokinin octapeptides (CCK8s) have been purified from methanol extracts of two brains from each of two Australian marsupials, Tammar Wallaby and Eastern Quoll, containing 3 nmol and 2 nmol of the peptides, respectively. Immunoreactive CCK was concentrated on QMA SepPak cartridges and purified by two successive ...
journal_title:Peptides
pub_type: 杂志文章
doi:10.1016/0196-9781(88)90280-x
更新日期:1988-03-01 00:00:00