Activation of GPR119 by fatty acid agonists augments insulin release from clonal β-cells and isolated pancreatic islets and improves glucose tolerance in mice.

Abstract:

:G-protein coupled receptor 119 (GPR119) is emerging as a potential target for the treatment of type 2 diabetes with beneficial effects on glucose homeostasis. This study assessed the insulin-secreting properties of various GPR119 agonists and the distribution of GPR119 in pancreatic islets. Endogenous ligands [oleoylethanolamide (OEA), palmitoylethanolamine (PEA)] and chemically synthetic analogues (AS-1269574, PSN-375963) were investigated in clonal BRIN-BD11 cells and mouse pancreatic islets. Secondary messenger assays such as intracellular Ca²⁺ and cAMP in response to agonists at normoglycaemic and hyperglycaemic conditions were assessed. Cytotoxicity was assessed by LDH release. AS-1269574 was the most potent and selective agonist tested in isolated islets, with an EC₅₀ value of 9.7×10⁻⁷ mol/l, enhancing insulin release maximally by 63.2%. Stimulation was also observed with GPR119 ligands; OEA (3.0×10⁻⁶ mol/l; 37.5%), PSN-375963 (2.4×10⁻⁶ mol/l; 28.7%) and PEA (1.2×10⁻⁶ mol/l; 22.2%). Results were corroborated by studies using BRIN-BD11 cells, which revealed augmentation of intracellular Ca²⁺ and cAMP. Both OEA and AS-1269574 enhanced insulin release and improved glucose tolerance in vivo in NIH Swiss mice. These results demonstrate the cellular localisation of GPR119 on islet cells (β and pancreatic polypeptide cells), its activation of the β-cell stimulus-secretion coupling pathway and glucose lowering effects in vivo.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Moran BM,Abdel-Wahab YH,Flatt PR,McKillop AM

doi

10.1515/hsz-2013-0255

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

453-64

issue

4

eissn

1431-6730

issn

1437-4315

pii

/j/bchm.just-accepted/hsz-2013-0255/hsz-2013-0255.

journal_volume

395

pub_type

杂志文章
  • Differential effects of novel tumour-derived p53 mutations on the transformation of NIH-3T3 cells.

    abstract::The p53 tumour suppressor gene is frequently mutated in human tumours and different tumour-derived mutations have varying effects on cells. The effect of a novel tumour-derived p53 mutation and two recently described mutations from South African breast cancer patients on the growth rate, colony formation, cell cycle a...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2008.010

    authors: Donninger H,Binder A,Bohm L,Parker MI

    更新日期:2008-01-01 00:00:00

  • Regulation of human cathepsin B by alternative mRNA splicing: homeostasis, fatal errors and cell death.

    abstract::One of the control mechanisms of cathepsin B biosynthesis and trafficking operates through alternative splicing of pre-mRNA. An mRNA lacking exon 2 is more efficiently translated than that containing all exons, and may be responsible for elevated biosynthesis and enzyme routing to the extracellular space, with critica...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/BC.2006.125

    authors: Baici A,Müntener K,Willimann A,Zwicky R

    更新日期:2006-08-01 00:00:00

  • Emerging roles for non-selenium containing ER-resident glutathione peroxidases in cell signaling and disease.

    abstract::Maintenance of cellular redox control is pivotal for normal cellular functions and cell fate decisions including cell death. Among the key cellular redox systems in mammals, the glutathione peroxidase (GPX) family of proteins is the largest conferring multifaceted functions and affecting virtually all cellular process...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2020-0286

    authors: Buday K,Conrad M

    更新日期:2020-10-22 00:00:00

  • GAPDH enhances group II intron splicing in vitro.

    abstract::Group II introns are autocatalytic RNAs which self-splice in vitro. However, in vivo additional protein factors might be involved in the splicing process. We used an affinity chromatography method called 'StreptoTag' to identify group II intron binding proteins from Saccharomyces cerevisiae. This method uses a hybrid ...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2004.076

    authors: Böck-Taferner P,Wank H

    更新日期:2004-07-01 00:00:00

  • Calcium-sensing receptor: roles in and beyond systemic calcium homeostasis.

    abstract::The cloning of a Ca2+(0)-sensing receptor (CaR) from parathyroid and kidney, coupled with the identification of inherited disorders in Ca2+(0)-sensing resulting from inactivating or activating mutations of this CaR, has provided substantial insights into how Ca2+(0) is regulated at a systemic level. The CaR plays a ce...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:

    authors: Chattopadhyay N,Vassilev PM,Brown EM

    更新日期:1997-08-01 00:00:00

  • The structural biology of the amyloid precursor protein APP - a complex puzzle reveals its multi-domain architecture.

    abstract::The amyloid precursor protein (APP) and its processing are widely believed to be central for the etiology of Alzheimer's disease (AD) and appear essential for neuronal development and cell homeostasis in mammals. Many studies show the proteolysis of APP by the proteases α-, β- and γ-secretase, functional aspects of th...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2013-0280

    authors: Coburger I,Hoefgen S,Than ME

    更新日期:2014-05-01 00:00:00

  • Septin functions in organ system physiology and pathology.

    abstract::Human septins comprise a family of 13 genes that encode for >30 protein isoforms with ubiquitous and tissue-specific expressions. Septins are GTP-binding proteins that assemble into higher-order oligomers and filamentous polymers, which associate with cell membranes and the cytoskeleton. In the last decade, much progr...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2013-0233

    authors: Dolat L,Hu Q,Spiliotis ET

    更新日期:2014-02-01 00:00:00

  • Chemistry and biochemistry of cold physical plasma derived reactive species in liquids.

    abstract::Reactive oxygen and nitrogen species deposited by cold physical plasma are proposed as predominant effectors in the interaction between discharge and biomedical application. Most reactive species found in plasma sources are known in biology for inter- and intracellular communication (redox signaling) and mammalian cel...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2018-0242

    authors: Wende K,von Woedtke T,Weltmann KD,Bekeschus S

    更新日期:2018-12-19 00:00:00

  • Assembly and function of small RNA - argonaute protein complexes.

    abstract::Small RNAs such as microRNAs (miRNAs), short interfering RNAs (siRNAs) or Piwi-interacting RNAs (piRNAs) are important regulators of gene expression in various organisms. Small RNAs bind to a member of the Argonaute protein family and are incorporated into larger structures that mediate diverse gene silencing events. ...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2014-0116

    authors: Dueck A,Meister G

    更新日期:2014-06-01 00:00:00

  • IGF-I receptor phosphorylation is impaired in cathepsin X-deficient prostate cancer cells.

    abstract::The cysteine-type peptidase cathepsin X is highly upregulated in several cancers and presumably promotes tumor invasion through bypassing cellular senescence. Here, we present first evidence that the underlying mechanism may involve the regulation of the insulin-like growth factor (IGF) system, a well-known activator ...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/hsz-2012-0209

    authors: Kraus S,Fruth M,Bunsen T,Nägler DK

    更新日期:2012-12-01 00:00:00

  • Activation of progelatinase A by mammalian legumain, a recently discovered cysteine proteinase.

    abstract::The activation of progelatinase A to gelatinase A requires cleavage of an asparaginyl bond to form the N-terminus of the mature enzyme. We have asked whether the activation can be mediated by legumain, the recently discovered lysosomal cysteine proteinase that is specific for hydrolysis of asparaginyl bonds. Addition ...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2001.093

    authors: Chen JM,Fortunato M,Stevens RA,Barrett AJ

    更新日期:2001-05-01 00:00:00

  • Identification and characterisation of C1q-binding phage displayed peptides.

    abstract::Five phage displayed peptide libraries were screened for binders to C1q, the recognition subunit of the classical complement pathway. Two rounds of panning resulted in the isolation and characterisation of several different phage displayed C1q-binding peptides from all five libraries. Two groups of the characterised p...

    journal_title:Biological chemistry

    pub_type: 评论,杂志文章

    doi:10.1515/bchm.1997.378.12.1509

    authors: Lauvrak V,Brekke OH,Ihle O,Lindqvist BH

    更新日期:1997-12-01 00:00:00

  • Differential distribution of four hyperpolarization-activated cation channels in mouse brain.

    abstract::Hyperpolarization-activated cation currents, termed I(h), are observed in a variety of neurons. Four members of a gene family encoding hyperpolarization-activated cyclic-nucleotide-gated cation channels (HCN1-4) have been cloned. The regional expression and cellular localization of the four HCN channel types in mouse ...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.1999.121

    authors: Moosmang S,Biel M,Hofmann F,Ludwig A

    更新日期:1999-07-01 00:00:00

  • Undersulfation of proteoheparan sulfate stimulates the expression of basic fibroblast growth factor and protein synthesis but suppresses replication of coronary smooth muscle cells.

    abstract::Heparan sulfate proteoglycans are obligatory for receptor binding and mitogenic activity of the basic fibroblast growth factor (bFGF). In the present study the influence of undersulfated heparan sulfate on the expression of basic fibroblast growth factor and coronary smooth muscle cell (cSMC) proliferation was investi...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/bchm.1997.378.7.701

    authors: Schriever C,Breithardt G,Schmidt A

    更新日期:1997-07-01 00:00:00

  • The pathobiochemistry of nitrogen dioxide.

    abstract::Nitrogen dioxide (*NO2) is an oxidizing free radical which can initiate a variety of destructive pathways in living systems, and several diseases are suspected to be connected with both exogenously and endogenously formed *NO2. Peroxynitrite (ONOO-/ONOOH) is believed to be an important endogenous source of *NO2 radica...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/BC.2002.043

    authors: Kirsch M,Korth HG,Sustmann R,de Groot H

    更新日期:2002-03-01 00:00:00

  • Structure and function of bacterial dynamin-like proteins.

    abstract::Membrane dynamics are essential for numerous cellular processes in eukaryotic and prokaryotic cells. In eukaryotic cells, membrane fusion and fission are often catalyzed by large GTPases of the dynamin protein family. These proteins couple GTP hydrolysis to membrane deformation, which eventually leads to fusion or fis...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2012-0185

    authors: Bramkamp M

    更新日期:2012-11-01 00:00:00

  • HIRIP3 is a nuclear phosphoprotein interacting with and phosphorylated by the serine-threonine kinase CK2.

    abstract::The HIRIP3 protein had been identified from its interaction with the HIRA histone chaperone. Experiments using anti-peptide antisera indicated that this 556-aa protein is nuclear throughout the cell cycle and excluded from condensed chromatin during mitosis. Based on its electrophoretic migration and sensitivity to ph...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2007.045

    authors: Assrir N,Filhol O,Galisson F,Lipinski M

    更新日期:2007-04-01 00:00:00

  • Amylin-induced cytotoxicity is associated with activation of caspase-3 and MAP kinases.

    abstract::Nanomolar concentrations of human amylin promote death of RINm5F cells in a time- and concentrationdependent manner. Morphological changes of chromatin integrity suggest that cells are predominantly undergoing apoptosis. Human amylin induces significant activation of caspase-3 and strong and sustained phosphorylation ...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2002.196

    authors: Rumora L,Hadzija M,Barisić K,Maysinger D,Grubiić TZ

    更新日期:2002-11-01 00:00:00

  • The non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase: biochemistry, structure, occurrence and evolution.

    abstract::The non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase catalyses the irreversible reaction of glyceraldehyde-3-phosphate to 3-phosphoglycerate by the reduction of NADP to NADPH. This is in contrast to the extensively analysed phosphorylating glyceraldehyde-3-phosphate dehydrogenases which catalyse the revers...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:

    authors: Habenicht A

    更新日期:1997-12-01 00:00:00

  • Self-organization versus Watchmaker: stochastic dynamics of cellular organization.

    abstract::The cell, as a molecular system, is often interpreted in terms of complex clockworks, and the design charts of mechanical and electrical engineering are assumed to provide adequate approximations for the description of cellular organization. However, a growing body of experimental evidence obtained through the observa...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/BC.2005.030

    authors: Kurakin A

    更新日期:2005-03-01 00:00:00

  • Mannose 6-phosphate receptor-dependent endocytosis of lysosomal enzymes is increased in sulfatide-storing kidney cells.

    abstract::Metachromatic leukodystrophy is a lysosomal disorder caused by the deficiency of arylsulfatase A (ASA). This leads to the storage of the sphingolipid 3-O-sulfogalactosylceramide (sulfatide) in various cell types, such as renal tubular cells. Examination of mannose 6-phosphate receptor (MPR300)-dependent endocytosis re...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2009.009

    authors: Klein D,Yaghootfam A,Matzner U,Koch B,Braulke T,Gieselmann V

    更新日期:2009-01-01 00:00:00

  • Calpastatin exon 1B-derived peptide, a selective inhibitor of calpain: enhancing cell permeability by conjugation with penetratin.

    abstract::The ubiquitous calpains, mu- and m-calpain, have been implicated in essential physiological processes and various pathologies. Cell-permeable specific inhibitors are important tools to elucidate the roles of calpains in cultivated cells and animal models. The synthetic N-acetylated 27-mer peptide derived from exon B o...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2003.045

    authors: Gil-Parrado S,Assfalg-Machleidt I,Fiorino F,Deluca D,Pfeiler D,Schaschke N,Moroder L,Machleidt W

    更新日期:2003-03-01 00:00:00

  • Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice.

    abstract::The ligand-activated aryl hydrocarbon receptor (AHR) is known to modulate many genes in a highly cell-specific manner, either directly or indirectly via secondary effects. In contrast, little is known about the effects of AHR deficiency on gene expression balance. We compared the transcriptome of CD4 T cells from AHR-...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2006.151

    authors: Frericks M,Temchura VV,Majora M,Stutte S,Esser C

    更新日期:2006-09-01 00:00:00

  • When, how and why? Regulated proteolysis by the essential FtsH protease in Escherichia coli.

    abstract::Cellular proteomes are dynamic and adjusted to permanently changing conditions by ATP-fueled proteolytic machineries. Among the five AAA+ proteases in Escherichia coli FtsH is the only essential and membrane-anchored metalloprotease. FtsH is a homohexamer that uses its ATPase domain to unfold and translocate substrate...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2016-0302

    authors: Bittner LM,Arends J,Narberhaus F

    更新日期:2017-05-01 00:00:00

  • Structure-function relationship of bromelain isoinhibitors from pineapple stem.

    abstract::Bromelain isoinhibitors from pineapple stem (BIs) are unique double-chain inhibitors and inhibit the cysteine proteinase bromelain competitively. The three-dimensional structure was shown to be composed of two distinct domains, each of which is formed by a three-stranded anti-parallel beta-sheet. Unexpectedly, BIs wer...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/BC.2002.126

    authors: Hatano K,Sawano Y,Tanokura M

    更新日期:2002-07-01 00:00:00

  • Efficacy of HOCl scavenging by sulfur-containing compounds: antioxidant activity of glutathione disulfide?

    abstract::Hypochlorous acid (HOCl) is a bactericidal compound formed by activated neutrophils during inflammation. Overproduction of HOCl causes damage to tissues at the site of neutrophil accumulation. The deleterious effects of excessive HOCl formation can be attenuated using antioxidants. Thiols and thioethers are known to b...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2002.073

    authors: den Hartog GJ,Haenen GR,Vegt E,van der Vijgh WJ,Bast A

    更新日期:2002-03-01 00:00:00

  • Inhibitory effect of the sugarcane cystatin CaneCPI-4 on cathepsins B and L and human breast cancer cell invasion.

    abstract::The lysosomal cysteine proteases cathepsin B and L play important roles in tumor cell invasion. An imbalance between these cathepsins and their endogenous inhibitors, the cystatins, has been associated with development of the metastatic phenotype. Accordingly, many studies have indicated potential use of cystatins in ...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2008.035

    authors: Gianotti A,Sommer CA,Carmona AK,Henrique-Silva F

    更新日期:2008-04-01 00:00:00

  • Eremophilane-type sesquiterpenes from fungi and their medicinal potential.

    abstract::Eremophilanes are sesquiterpenes with a rearranged carbon skeleton formed both by plants and fungi, however, almost no plant eremophilanes are found in fungi. These eremophilanes possess mainly phytotoxic, antimicrobial, anticancer and immunomodulatory properties and in this review fungal eremophilanes with bioactivit...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2017-0171

    authors: Yuyama KT,Fortkamp D,Abraham WR

    更新日期:2017-12-20 00:00:00

  • High activity of the calcineurin A subunit with a V314 deletion.

    abstract::A deletion mutant (V314) of the calcineurin A subunit was constructed using site-directed mutagenesis. Its phosphatase activity and function were then characterized. The V314 deletion significantly altered the phosphatase activity, which was more than ten times higher than that of wild-type calcineurin, the calcineuri...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.1999.163

    authors: Yan L,Wei Q

    更新日期:1999-11-01 00:00:00

  • The miRNA-kallikrein axis of interaction: a new dimension in the pathogenesis of prostate cancer.

    abstract::Kallikrein-related peptidases (KLKs) are a family of serine proteases that were shown to be useful cancer biomarkers. KLKs have been shown to be dysregulated in prostate cancer (PCa). microRNAs (miRNAs) are short RNA nucleotides that negatively regulate gene expression and have been reportedly dysregulated in PCa. We ...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/hsz-2011-0246

    authors: White NM,Youssef YM,Fendler A,Stephan C,Jung K,Yousef GM

    更新日期:2012-04-01 00:00:00