Dipeptidyl peptidase-4 impairs insulin signaling and promotes lipid accumulation in hepatocytes.

Abstract:

:Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signaling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively. Additionally, glucose-6-phosphatase cDNA expression was significantly decreased in DPP-4 deficiency. Reduced triglyceride content in DPP-4 knockdown cells was paralleled by enhanced expressions of peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase -1 (CPT-1) while sterol regulatory element-binding protein 1c (SREBP-1c) expression was significantly decreased. Our data suggest that hepatic DPP-4 induces a selective pathway of insulin resistance with reduced glycogen storage, enhanced glucose output and increased lipid accumulation in the liver. Hepatic DPP-4 might be a novel target in fatty liver disease in patients with glucose intolerance.

authors

Rufinatscha K,Radlinger B,Dobner J,Folie S,Bon C,Profanter E,Ress C,Salzmann K,Staudacher G,Tilg H,Kaser S

doi

10.1016/j.bbrc.2017.02.071

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

366-371

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(17)30352-2

journal_volume

485

pub_type

杂志文章
  • Lupeol induces p53 and cyclin-B-mediated G2/M arrest and targets apoptosis through activation of caspase in mouse skin.

    abstract::Lupeol, present in fruits and medicinal plants, is a biologically active compound that has been shown to have various pharmacological properties in experimental studies. In the present study, we demonstrated the modulatory effect of lupeol on 7,12-dimethylbenz[a]anthracene (DMBA)-induced alterations on cell proliferat...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2009.02.033

    authors: Nigam N,Prasad S,George J,Shukla Y

    更新日期:2009-04-03 00:00:00

  • Blocking antibodies specific for human albumin interfere with the hemolytic activity of the membrane attack complex of complement.

    abstract::Earlier, we showed that antibodies specific for human serum albumin are able to bind to erythrocyte-associated albumin and inhibit complement mediated hemolysis. In the present study we determine if inhibition is occurring at the membrane attack phase of complement activation or at an earlier step. We show that althou...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.1994.1425

    authors: Houle JJ,Hoffmann EM

    更新日期:1994-04-15 00:00:00

  • Active fragments and analogs of the insect neuropeptide leucopyrokinin: structure-function studies.

    abstract::Evaluation of analogs of the blocked insect myotropic neuropeptide leucopyrokinin (LPK) has demonstrated its relative insensitivity to amino acid substitution in the N-terminal in contrast to the C-terminal region. Truncated analogs of LPK without the first, second, and third N-terminal amino acids retain a significan...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/0006-291x(86)90315-3

    authors: Nachman RJ,Holman GM,Cook BJ

    更新日期:1986-06-30 00:00:00

  • Sugarcane Elongin C is involved in infection by sugarcane mosaic disease pathogens.

    abstract::Sugarcane (Saccharum sp. hybrid) provides the main source of sugar for humans. Sugarcane mosaic disease (SMD) is a major threat to sugarcane production. Currently, control of SMD is mainly dependent on breeding resistant cultivars through hybridization, which is time-consuming. Understanding the mechanism of viral inf...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2015.09.015

    authors: Zhai Y,Deng Y,Cheng G,Peng L,Zheng Y,Yang Y,Xu J

    更新日期:2015-10-23 00:00:00

  • The stress-activated c-Jun protein kinase (JNK) is stimulated by lipoxygenase pathway product 12-HETE in RIN m5F cells.

    abstract::Cytokine induced pancreatic beta-cell destruction seen in Type 1 diabetes and islet graft rejection involves multiple intracellular signaling pathways that directly or indirectly lead to inflammatory damage or programmed cell death. IL-1beta has been shown to stimulate the 12-lipoxygenase pathway product 12-HETE, in R...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.1996.5981

    authors: Bleich D,Chen S,Wen Y,Nadler JL

    更新日期:1997-01-13 00:00:00

  • Retinoic acid-induced differentiation-specific, C-kinase-dependent phosphorylation of cytosolic 44 and 32 kDa proteins in HL-60 cells.

    abstract::The effect of various differentiation-inducers on the activity of Ca2+, phospholipid-dependent protein kinase (C-kinase) activity and endogenous protein phosphorylation by the kinase were examined in the extracts of HL-60 cells. Although all of the inducers, retinoic acid, dibutyryl cAMP, nicotinamide, dimethylsulfoxi...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/0006-291x(90)91163-m

    authors: Tanaka Y,Tsuyuki M,Itaya-Hironaka A,Inada Y,Yoshihara K,Kamiya T

    更新日期:1990-05-16 00:00:00

  • Atorvastatin induces tissue transglutaminase in human endothelial cells.

    abstract::Tissue transglutaminase (tTgase) contributes to the organisation of the basement membrane and is therefore thought to be important for the integrity and stability of the vessel wall. In the present study, we hypothesised that the HMG-CoA reductase inhibitor atorvastatin may up-regulate the tTgase expression in endothe...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2004.07.087

    authors: Soehnlein O,Eskafi S,Schmeisser A,Kloos H,Daniel WG,Garlichs CD

    更新日期:2004-09-10 00:00:00

  • High glucose induced VEGF expression via PKC and ERK in glomerular podocytes.

    abstract::Podocytes are the major site of vascular endothelial growth factor (VEGF) production in the kidney, and up-regulation of VEGF plays a critical role in the progression of diabetic nephropathy. Using a differentiated mouse podocyte cell line, we investigated the roles of protein kinase C (PKC) and extracellular signal-r...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.2001.6138

    authors: Hoshi S,Nomoto K,Kuromitsu J,Tomari S,Nagata M

    更新日期:2002-01-11 00:00:00

  • NF-kappaB functions in osteoclasts.

    abstract::NF-kappaB is a pleiotropic transcription factor, which regulates osteoclast formation, function, and survival. The finding that the deletion of both NF-kappaB p50 and p52 subunits resulted in osteopetrosis due to the absence of osteoclasts was followed by the observation that NF-kappaB is essential for RANK-expressing...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章,评审

    doi:10.1016/j.bbrc.2008.10.146

    authors: Soysa NS,Alles N

    更新日期:2009-01-02 00:00:00

  • Spore-displayed streptavidin: a live diagnostic tool in biotechnology.

    abstract::Streptavidin, which is one of the most widely used proteins in biotechnological application field and is active only in tetrameric form, was surface expressed on the surface of Bacillus subtilis spore. Spore coat protein of B. subtilis, CotG, was used as an anchoring motif to display streptavidin. FACS using anti-stre...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2005.03.144

    authors: Kim JH,Lee CS,Kim BG

    更新日期:2005-05-27 00:00:00

  • Identification of anti-TNFalpha peptides with consensus sequence.

    abstract::Phage displayed peptide library was used to select tumor necrosis factor alpha (TNFalpha) binding peptides. After three sequential rounds of biopanning, some linear TNFalpha-binding peptides were identified from a 12-mer peptide library. A consensus sequence (L/M)HEL(Y/F)(L/M)X(W/Y/F), where X might be variable residu...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2003.09.141

    authors: Zhang J,Zheng L,Zhao A,Gao B,Liu NL,Wang F,Dong J,Xin ZT,Shao NS,Wang HX,Xue YN

    更新日期:2003-10-31 00:00:00

  • Upregulation of 24(R/S),25-epoxycholesterol and 27-hydroxycholesterol suppresses the proliferation and migration of gastric cancer cells.

    abstract::Gastric cancer (GC) is one of the most common cancers and is the second-leading cause of cancer-associated morbidity worldwide. Oxysterols are oxidized derivatives of cholesterol that may be important in many biological processes, but the levels and roles of oxysterols in gastric tumours remain to be elucidated. The l...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2018.09.058

    authors: Guo F,Hong W,Yang M,Xu D,Bai Q,Li X,Chen Z

    更新日期:2018-10-12 00:00:00

  • Paradoxical stabilization of the neutral flavin semiquinone of xanthine dehydrogenase at high pH.

    abstract::The pH dependence of the behavior of chicken liver xanthine dehydrogenase in the course of reductive titrations with sodium dithionite has been examined. Below pH 8.5, the behavior of xanthine dehydrogenase is similar to that of the much better understood milk xanthine oxidase, with the amount of neutral semiquinone a...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.1993.1934

    authors: Ratnam K,Hille R

    更新日期:1993-08-16 00:00:00

  • Leucine-rich repeat-containing G-protein coupled receptor 5 enriched organoids under chemically-defined growth conditions.

    abstract::An organoid is a complex, multi-cell three-dimensional (3D) structure that contains tissue-specific cells. Epithelial stem cells, which are marked by leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), have the potential for self-renewal and expansion as organoids. However, in the case of intestinal or...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2018.11.003

    authors: Hahn S,Kim MS,Choi SY,Jeong S,Jee J,Kim HK,Jeong SY,Shin H,Kim HS,Park JS,Yoo J

    更新日期:2019-01-08 00:00:00

  • Inositol tetrakisphosphates as second messengers induce Ca(++)-dependent chloride currents in Xenopus laevis oocytes.

    abstract::Microinjection of inositol 1,3,4,5-tetrakisphosphate or inositol 1,4,5-trisphosphate induced distinct chloride membrane currents in defolliculated Xenopus laevis oocytes. To decide whether these Cl(-)-currents were due to the injected compounds or their metabolic products, [3H]Ins(1,3,4,5)P4 or [3H]Ins(1,4,5)P3 were i...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/0006-291x(91)91420-h

    authors: Guse AH,Gercken G,Boysen H,Schwarz JR,Meyerhof W

    更新日期:1991-08-30 00:00:00

  • Induction of c-fos transcription in the medaka brain (Oryzias latipes) in response to mating stimuli.

    abstract::Immediate-early genes (IEGs) are useful for mapping active brain regions in various vertebrates. Here we identified a c-fos homologue gene in medaka and demonstrated that the amounts of c-fos transcripts and proteins in the medaka brain increased in relation to an artificially evoked seizure, suggesting that the homol...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2010.11.143

    authors: Okuyama T,Suehiro Y,Imada H,Shimada A,Naruse K,Takeda H,Kubo T,Takeuchi H

    更新日期:2011-01-07 00:00:00

  • Diphenyleneiodonium enhances oxidative stress and inhibits Japanese encephalitis virus induced autophagy and ER stress pathways.

    abstract::Diphenyleneiodonium (DPI) and N-acetyl-l-cysteine (NAC), two widely used anti-oxidants, were employed to evaluate the role of oxidative stress in Japanese encephalitis virus (JEV) induced autophagy, stress responses and replication. DPI and NAC exerted opposite effects on ROS levels in JEV infected mouse neuronal cell...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2018.05.149

    authors: Sharma M,Sharma KB,Chauhan S,Bhattacharyya S,Vrati S,Kalia M

    更新日期:2018-07-12 00:00:00

  • Anabolic five subunit-type pyruvate:ferredoxin oxidoreductase from Hydrogenobacter thermophilus TK-6.

    abstract::The thermophilic, obligately chemolithoautotrophic hydrogen-oxidizing bacterium, Hydrogenobacter thermophilus TK-6, assimilates carbon dioxide via the reductive tricarboxylic acid cycle. A gene cluster, porEDABG, encoding pyruvate:ferredoxin oxidoreductase (POR), which plays a key role in this cycle, was cloned and se...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2005.11.155

    authors: Ikeda T,Ochiai T,Morita S,Nishiyama A,Yamada E,Arai H,Ishii M,Igarashi Y

    更新日期:2006-02-03 00:00:00

  • Narrow leaf 1 (NAL1) regulates leaf shape by affecting cell expansion in rice (Oryza sativa L.).

    abstract::The narrow leaf1 (nal1) mutant of rice (Oryza sativa L.) exhibits a narrow leaf phenotype. Previous studies have shown that NAL1 modulates leaf size by affecting vein patterning and cell division; however, the underlying mechanism remains unclear. Here, we report that the nal1 mutant shows reduced size of the leaf aba...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2019.06.142

    authors: Lin L,Zhao Y,Liu F,Chen Q,Qi J

    更新日期:2019-08-27 00:00:00

  • Human macrophages produce dimeric forms of IL-18 which can be detected with monoclonal antibodies specific for inactive IL-18.

    abstract::We established two monoclonal antibodies (mAbs) which specifically recognize human 'functionally inactive' recombinant IL-18, and IL-18 protein polymorphism was examined using human monocytes and macrophages (M phi). In 6 day GM-CSF-treated M phi, an 'inactive' IL-18-recognizing mAb 21 detected the IL-18 proform (24 k...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.2001.4378

    authors: Kikkawa S,Matsumoto M,Shida K,Fukumori Y,Toyoshima K,Seya T

    更新日期:2001-02-23 00:00:00

  • TTX displacement of [H3]-nitrendipine binding in developing spinal cord neurons.

    abstract::[3H] Nitrendipine binding was partially blocked by the presence of tetrodotoxin in developing spinal cord neurons. In young cultures, 1 micron tetrodotoxin displaced 29% and 26% of [3H] nitrendipine binding from the high and low affinity binding sites, respectively. In one month old cultures, tetrodotoxin had no effec...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/0006-291x(84)91054-4

    authors: Litzinger MJ,Brenneman DE

    更新日期:1984-11-14 00:00:00

  • Support for a potential role of E. coli oligopeptidase A in protein degradation.

    abstract::Protein degradation is an essential quality control and regulatory function in organisms ranging from bacteria to eukaryotes. In bacteria, this process is initiated by ATP-dependent proteases which digest proteins to short peptides that are subsequently hydrolyzed to smaller fragments and free amino acids. While the e...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2007.05.142

    authors: Jain R,Chan MK

    更新日期:2007-08-03 00:00:00

  • Activation of the Wnt/β-catenin pathway in pancreatic beta cells during the compensatory islet hyperplasia in prediabetic mice.

    abstract::The Wnt/β-catenin signaling pathway, also known as the canonical Wnt pathway, plays a role in cell proliferation and differentiation in several tissues/organs. It has been recently described in humans a relationship between type 2 diabetes (T2DM) and mutation in the gene encoding the transcription factor TCF7L2 associ...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2016.08.146

    authors: Maschio DA,Oliveira RB,Santos MR,Carvalho CP,Barbosa-Sampaio HC,Collares-Buzato CB

    更新日期:2016-09-30 00:00:00

  • EGCG inhibits activation of the insulin-like growth factor-1 receptor in human colon cancer cells.

    abstract::The IGF/IGF-1R system, which includes the IGF, IGF-1R, and IGFBPs proteins, plays an important role in the development and growth of colorectal cancer. We previously reported that in the HT29 human colon cancer cell line EGCG, the major biologically active component of green tea, inhibits activation of the RTKs EGFR, ...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2005.06.182

    authors: Shimizu M,Deguchi A,Hara Y,Moriwaki H,Weinstein IB

    更新日期:2005-09-02 00:00:00

  • Structural characterization of thymidine phosphorylase purified from human placenta.

    abstract::Human thymidine phosphorylase (dThdPase) is thought to be identical to an angiogenesis factor, platelet-derived endothelial cell growth factor (PD-ECGF). However, the whole amino acid sequence of dThdPase is still unknown. N-terminal amino acid sequencing of dThdPase isolated from human placenta gave the sequence Ac-A...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.1995.2074

    authors: Miyadera K,Dohmae N,Takio K,Sumizawa T,Haraguchi M,Furukawa T,Yamada Y,Akiyama S

    更新日期:1995-07-26 00:00:00

  • Effect of phosphorylation on 68 KDa neurofilament subunit protein assembly by the cyclic AMP dependent protein kinase in vitro.

    abstract::The effect of phosphorylation by cyclic AMP dependent protein kinase on the assembly of the core-forming 68 KDa neurofilament subunit protein (NF-L) was studied in vitro by fluorescence energy transfer and electron microscopy. Phosphorylation of unassembled NF-L in a low ionic strength buffer by cyclic AMP dependent p...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/0006-291x(90)90394-3

    authors: Nakamura Y,Takeda M,Angelides KJ,Tanaka T,Tada K,Nishimura T

    更新日期:1990-06-15 00:00:00

  • Multi-frequency EPR evidence for a binuclear CuA center in cytochrome c oxidase: studies with a 63Cu- and 65Cu-enriched, soluble domain of the cytochrome ba3 subunit II from Thermus thermophilus.

    abstract::We have recorded multi-frequency EPR spectra of 63Cu- and 65Cu-labeled, water-soluble CuA-protein from the cytochrome ba3 of T. thermophilus. The spectrum taken at the highest frequency (34.03 GHz) shows no hyperfine structure and is nominally axial with apparent gz approximately 2.18 and gxy approximately 2.00. The s...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.1995.1938

    authors: Fee JA,Sanders D,Slutter CE,Doan PE,Aasa R,Karpefors M,Vänngård T

    更新日期:1995-07-06 00:00:00

  • Knockdown of astrocyte elevated gene-1 inhibits tumor growth and modifies microRNAs expression profiles in human colorectal cancer cells.

    abstract::Astrocyte elevated gene-1 (AEG-1), upregulated in various types of malignancies including colorectal cancer (CRC), has been reported to be associated with the carcinogenesis. MicroRNAs (miRNAs) are widely involved in the initiation and progression of cancer. However, the functional significance of AEG-1 and the relati...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2014.01.046

    authors: Huang S,Wu B,Li D,Zhou W,Deng G,Zhang K,Li Y

    更新日期:2014-02-14 00:00:00

  • Toosendanin induces caspase-dependent apoptosis through the p38 MAPK pathway in human gastric cancer cells.

    abstract::Although many advances have been made in the treatment of gastric cancer (GC), numerous difficulties, such as the emergence of chemo-drug resistance, continue to lead to disappointing GC prognoses. Thus, novel alternative strategies are urgently needed. The use of natural products could be a viable option to treat GC....

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2018.09.093

    authors: Zhou Q,Wu X,Wen C,Wang H,Wang H,Liu H,Peng J

    更新日期:2018-10-20 00:00:00

  • KLHL2 interacts with and ubiquitinates WNK kinases.

    abstract::Mutations in the WNK1 and WNK4 genes result in an inherited hypertensive disease, pseudohypoaldosteronism type II (PHAII). Recently, the KLHL3 and Cullin3 genes were also identified as responsible genes for PHAII. Although we have reported that WNK4 is a substrate for the KLHL3-Cullin3 E3 ligase complex, it is not cle...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2013.06.104

    authors: Takahashi D,Mori T,Wakabayashi M,Mori Y,Susa K,Zeniya M,Sohara E,Rai T,Sasaki S,Uchida S

    更新日期:2013-08-02 00:00:00