Abstract：
AIM:To study the effect of chronic insulin treatment on insulin post-receptor signaling transduction and whether the effects of metformin are transmitted throughout the cascade of insulin signaling intermediates in a human hepatoma cell line (Hep G2). METHODS:Hep G2 cells were incubated in serum free media containing either insulin 100 nmol/L or insulin 100 nmol/L plus different concentrations (0.01-10 mmol/L) of metformin for 16 h and then were stimulated with insulin 100 nmol/L for 1 min. RESULTS:Chronic treatment of insulin 100 nmol/L induced a significant reduction in the phosphorylation and protein expression of IR?, IRS1 and IRS2, which therefore resulted in a downregulation of association of PI3K with IRS. Therapeutic concentrations (0.01-0.1 mmol/L) of metformin prevented the changes induced by chronic insulin treatment in these post-receptor components of insulin signaling pathway. Tyrosine phosphorylation of IR?, IRS1, and IRS2 was increased by 2.7 fold (P < 0.01), 6.8 fold (P < 0.01), and 2.3 fold (P <0.01) of chronically insulin-treated cells alone, respectively, after metformin 0.1 mmol/L was added. The association of p85 with IRS1 and IRS2 was also increased from 34 % to 86 % (P <0.01) and from 30 % to 92 % (P <0.01), respectively. In contrast, metformin in pharmacological concentration (1-10 mmol/L) further inhibited tyrosine phosphorylation of IR?, IRS1, IRS2 and the interaction of PI3K with IRS. The association of IRS1 with p85 was further decreased by 58 % (P >0.05) and of IRS2 by 30 % (P <0.05). CONCLUSION:Chronic insulin exposure of Hep G2 cells induces the downregulation of insulin signal transduction via PI3K pathway. The effect of metformin on insulin signaling transduction represent a primary mechanism of metformin action in insulin resistant state.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Yuan L,Ziegler R,Hamann Asubject
Has Abstractpub_date
2003-01-01 00:00:00pages
55-60issue
1eissn
1671-4083issn
1745-7254journal_volume
24pub_type
杂志文章abstract：AIM:To explore whether the differential effects of Zn2+ on ryanodine binding to the sarcoplasmic reticulum (SR) of skeletal and cardiac muscles resulted from different permeability of the SR to Zn2+. METHODS:[3H]ryanodine binding assays were performed to examine the effect of Zn2+ on ryanodine binding to the SR in the...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-12-01 00:00:00
abstract：AIM:To investigate the mechanisms underlying the isomer-selective distribution of 3-n-butylphthalide (NBP) hydroxylated metabolites, 3-hydroxy-NBP (3-OH-NBP) and 10-hydroxy-NBP (10-OH-NBP), across the blood brain barrier (BBB). METHODS:After oral administration of NBP (20 mg/kg) to rats, the pharmacokinetics of two ma...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2015.64
更新日期：2015-12-01 00:00:00
abstract：AIM:To study whether urotensin II (UII), a potent vasoconstrictive peptide, is involved in the development of cardiac hypertrophy and fibrogenesis of rats induced by isoproterenol (ISO). METHODS:Thirty male Wistar rats were randomly divided into 3 groups. Group 1 was the healthy control group, group 2 was the ISO grou...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00485.x
更新日期：2007-01-01 00:00:00
abstract：AIM:To investigate the expression of c-Met in peritoneal free cancer cells isolated from human gastric cancer ascites, and its relationship to peritoneal dissemination of gastric cancer. METHODS:Peritoneal free cancer cells (PFCCs) were isolated from ascites specimens of gastric cancer patients. c-Met expression in PF...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2011.205
更新日期：2012-04-01 00:00:00
abstract：AIM:Breviscapine isolated from the Chinese herb Erigeron breviscapus (Vant) Hand-Mazz is widely used to treat cardiovascular and cerebrovascular diseases. The aim of this study was to improve the pharmacokinetic profiles of breviscapine using nanostructured lipid carrier based on an ionic complex formation. METHODS:Br...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2013.43
更新日期：2013-08-01 00:00:00
abstract：AIM:To determine the Ca2+ source and cellular mechanisms of spontaneous Ca2+ oscillations in hippocampal astrocytes. METHODS:The cultured cells were loaded with Fluo-4 AM, the indicator of intracellular Ca2+, and the dynamic Ca2+ transients were visualized with confocal laser-scanning microscopy. RESULTS:The spontane...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2006.00397.x
更新日期：2006-07-01 00:00:00
abstract：AIM:Catechol estrogens and 16alpha-hydroxy estrogen are important metabolites that cause carcinogenesis. This study was aimed to stud y the role of cytochrome P450 in estradiol metabolism. METHODS:The estradiol metabolites were determined with HPLC-ECD. Correlation of estradiol metabolites production between cytochrom...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2001-02-01 00:00:00
abstract：:Diabetic nephropathy (DN) is characterized by sterile inflammation with continuous injury and loss of renal inherent parenchyma cells. Podocyte is an essential early injury target in DN. The injury and loss of podocytes are closely associated with proteinuria, the early symptom of renal injury in DN. However, the exac...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-020-00525-z
更新日期：2020-09-23 00:00:00
abstract：:Wound healing impairment represents a particularly challenging clinical problem to which no efficacious treatment regimens currently exist. The factors ensuring appropriate intercellular communication during wound repair are not completely understood. Although protein-type mediators are well-established players in thi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1111/j.1745-7254.2005.00058.x
更新日期：2005-03-01 00:00:00
abstract：AIM:To investigate whether or not brain histamine was involved in memory deficits induced by lesions of nucleus basalis magnocellularis (NBM) in rats. METHODS:Passive avoidance response was used to measure memory process in rats, and NBM was bilaterally lesioned by injection of ibotenic acid (6 microg/site). RESULTS:...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-01-01 00:00:00
abstract：AIM:To investigate the antitumor actions of the Crotalus durissus neurotoxin (crotoxin) on human esophageal carcinoma (Eca-109) cells in vitro and transplanted esophageal Eca-109 tumors in nude mice. METHODS:The growth-inhibitory effect was analyzed in Eca-109 cells using MTT assay. Cell morphology changes in nuclei w...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2012.156
更新日期：2013-02-01 00:00:00
abstract：AIM:To study the effects of dl-praeruptorin A (Pd-Ia) on nucleus factor-kappaB (NF-kappaB) activativity and tumor necrosis factor-alpha (TNF-alpha) expression in ischemia-reperfusion (I/R) myocardium. METHODS:Langendorff's isolated rat heart was subjected to a 10-min ischemia followed by a 30-min reperfusion. NF-kappa...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-01-01 00:00:00
abstract：AIM:To investigate the influence of picroside II on hepatocyte apoptosis and its mechanism. METHODS:Morphological changes and quantification of apoptotic cells were determined under transmission electron microscopy and flow cytometry respectively. DNA fragmentation was visualized by agarose gel electrophoresis. Semi-q...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2005.00729.x
更新日期：2005-06-01 00:00:00
abstract：:Top down central nervous system (CNS) influences on the immune system and bottom up immune system influences on the CNS take part in a complex feedforward and feedback loop which may be responsible for initiating events and perpetuating circumstances in the course of neuropsychiatric as well as immune system diseases....
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：
更新日期：2001-07-01 00:00:00
abstract：AIM:To study the influence of angiotensin (Ang) II receptor antagonist (AT1) valsartan and angiotensin-converting enzyme (ACE) inhibitor fosinopril on the cardiac hypertrophy induced by catecholamine. METHODS:A cardiac hypertrophy model was produced by i.p. norepinephrine (NE) 1.5 mg.kg-1.d-1 x 15 d. The animals were ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2000-09-01 00:00:00
abstract：:Conjugated polymer nanomaterials (CPNs), as optically and electronically active materials, hold promise for biomedical imaging and drug delivery applications. This review highlights the recent advances in the utilization of CPNs in theranostics. Specifically, CPN-based in vivo imaging techniques, including near-infrar...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2017.42
更新日期：2017-06-01 00:00:00
abstract：:Severe acute pancreatitis (SAP) is a severe acute abdominal disease. Recent evidence shows that intestinal homeostasis is essential for the management of acute pancreatitis. Chitosan oligosaccharides (COS) possess antioxidant activity that are effective in treating various inflammatory diseases. In this study we explo...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-020-00581-5
更新日期：2021-01-25 00:00:00
abstract：AIM:Using sparse data of valproate (VPA) serum concentrations to build a population pharmacokinetic (PPK) model of VPA in Chinese children with epilepsy and to predict serum concentrations for new patients using a Bayesian approach. METHODS:Two hundred epileptic children, whose VPA serum concentrations were collected,...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-12-01 00:00:00
abstract：AIM:To evaluate the efficiency of 3 short hairpin RNA (shRNA) interfering with the herpes simplex virus type 1 (HSV-1) gene coding glycoprotein D (gD) for inhibiting the gD expression and virus replication in vitro. METHODS:Vero cells were selected for an in vitro model of infection. Three shRNA sequences (shRNAgD1, -...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00828.x
更新日期：2008-08-01 00:00:00
abstract：AIM:To discover novel cell division cycle 25 (CDC25) B inhibitors and elucidate the mechanisms of inhibition in cancer cells. METHODS:Cell growth inhibition was detected by MTT assay, the cell cycle was analyzed by flow cytometry, and protein expression and phosphorylation was examined by Western blot analysis. RESUL...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2009.131
更新日期：2009-09-01 00:00:00
abstract：:Dry eye disease (DED) is a multifactorial disorder of the tears and ocular surface characterized by manifestations of dryness and irritation. Although the pathogenesis is not fully illuminated, it is recognized that inflammation has a prominent role in the development and deterioration of DED. β-aminoarteether maleate...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-020-0484-5
更新日期：2020-08-03 00:00:00
abstract：AIM:The feasibility of inducing endocrine pancreatic differentiation of embryonic stem (ES) cells has been well documented. However, whether ES cells possess the potential for exocrine pancreatic differentiation requires further exploration. Here, we investigated whether sodium butyrate and glucocorticoids were conduci...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2009.115
更新日期：2009-09-01 00:00:00
abstract：AIM:To develop and validate a novel precolumn derivatization method for the quantitative determination and pharmacokinetic application of acetylshikonin in macaque monkeys by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). METHODS:2-Mercaptoethanol was added to the blood sample a...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00898.x
更新日期：2008-12-01 00:00:00
abstract：AIM:To investigate the effect of incorporation of an isoleucine zipper (IZ) motif into CD40 on binding activity of CD40 for the CD40 ligand (CD40L). METHODS:Prokaryotic expression vectors for 2 soluble CD40 derivatives, shCD40His and shCD40IZ containing an IZ domain, were constructed and expressed in Escherichia coli....
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2006.00285.x
更新日期：2006-03-01 00:00:00
abstract：AIM:To evaluate the therapeutic effects of gamichunggantang (GCT) on hyperlipidemia through high cholesterol diet model. GCT is an Oriental herbal medication, which has been used for the treatment of fatty liver, hyperlipidemia or alcoholic liver disease in Daejeon University Oriental Hospital, Korea since 1999. METHO...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2003-02-01 00:00:00
abstract：AIM:To study the effects and mechanisms by which hyposmotic challenge modulate function of L-type calcium current (I(Ca,L)) in rat ventricular myocytes. METHODS:The whole-cell patch-clamp techniques were used to record I(Ca,L) in rat ventricular myocytes. RESULTS:Hyposmotic challenge(∼220 mosmol/L) induced biphasic c...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2010.112
更新日期：2010-11-01 00:00:00
abstract：AIM:To examine the protective effect of propofol in renal ischemia/reperfusion (I/R) injury and the role of heme oxygenase-1 (HO-1) in this process. METHODS:Sprague-Dawley rats were randomly divided into 3 groups: (i) sham-operated group; (ii) I/R group; and (iii) propofol group. Bilateral renal warm ischemia for 45 m...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00566.x
更新日期：2007-08-01 00:00:00
abstract：AIM:To explore the action of doxorubicin on vascular smooth muscle cells. METHODS:Isometric tension of denuded or intact thoracic aortic vessels was recorded and [Ca(2+)](i) in isolated aortic smooth muscle cells was measured by using Fluo-3. RESULTS:Doxorubicin induced phasic and tonic contractions in denuded vessel...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2009.145
更新日期：2009-11-01 00:00:00
abstract：AIM:NLRP3 inflammasome plays an important role in renal injury and may be a therapeutic target in the treatment of patients with progressive chronic kidney disease. In this study we investigated whether angiotensin II (Ang II)-induced NLRP3 inflammasome activation was linked to endoplasmic reticulum stress (ERS) in hum...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2015.21
更新日期：2015-07-01 00:00:00
abstract：AIM:To study the effect of chloroquine on the expression of human clotting factor IX (hFIX) in mice. METHODS:Hydrodynamics-based naked DNA plasmid administration was performed by tail vein injection of 10 microg of pCMV- hFIX and chloroquine (0, 100, 200, and 500 micromol/L) in 2.2 mL of Ringer's solution within 6-7 s...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-05-01 00:00:00
