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INS — SERPINE1
Pathways - manually collected, often from reviews:
Text-mined interactions from Literome
Morange et al., Diabetes 1999
:
These results support the hypothesis that
PAI-1 expression in human adipose tissue is
controlled by
insulin and glucocorticoids and may help to explain the increase in plasma PAI-1 levels observed in patients with android obesity
Sakamoto et al., Am J Physiol 1999
:
Because induction of
PAI-1 by TNF-alpha is
potentiated synergistically by
insulin , both agonists appear likely to contribute to the impairment of fibrinolytic system capacity typical in obese, hyperinsulinemic patients
Galajda et al., Vnitr Lek 1999
(Diabetes Mellitus...) :
Insulin inhibits induced endothelial
PAI-1 production
Grenett et al., Thromb Haemost 1999
(Genetic Predisposition to Disease...) :
In order to determine whether
insulin regulates
PAI-1 expression in a genotype-specific manner, individual human umbilical vein ECs ( HUVECs ) were genotyped using a Hind III RFLP and incubated in the absence/presence of insulin ... Treatment of HUVECs with actinomycin D or puromycin completely abolished the
induction of
PAI-1 by
insulin
Mussoni et al., Ann Med 2000
(Hyperlipidemias) :
In contrast, the
increase of
PAI-1 with rising
insulin levels was evident in the highest triglyceride tertile
Koistinen et al., Diabetes Metab Res Rev 2000
(Diabetes Mellitus...) :
Subcutaneous adipose tissue
PAI-1 mRNA expression is not acutely
regulated by
insulin , and it is subject to a diurnal variation
Crandall et al., Biochem Biophys Res Commun 2000
:
Release of
PAI-1 by human preadipocytes and adipocytes
independent of
insulin and IGF-1 ...
Insulin and IGF-1 over a range of concentrations
had no effect on
PAI-1 release, and RT-PCR of PAI-1 mRNA following treatment with insulin and IGF-1 also indicated similar expression between treatments
Sudi et al., J Pediatr Endocrinol 2001
(Insulin Resistance...) :
Insulin and tPA-Ag
contributed to
PAI-1 ( adj. R2 = 0.36, p < 0.0001 ), whereas percentage fat mass and triglycerides contributed to tPA-Ag ( adj. R2 = 0.469, p < 0.0001 )
Banfi et al., Diabetes 2001
(Carcinoma, Hepatocellular...) :
These results outline the central role of MAP kinase activation in the regulation of
PAI-1 induced by
insulin
Seki et al., J Cell Physiol 2001
:
Insulin , IBMX, and dexamethasone significantly decreased both uPA and tPA production, and
increased PAI-1 production
Mondal et al., AIDS Res Hum Retroviruses 2001
:
The
insulin mediated
induction ( 3- to 4-fold ) of
PAI-1 and PAI-2 message was suppressed on exposure to PIs, which was reversed by troglitazone treatment
Vulin et al., J Biol Chem 2002
:
Insulin increases
PAI-1 production in several experimental systems, but the mechanism of insulin activated PAI-1 transcription remains to be determined
Banfi et al., Minerva Endocrinol 2002
(Cardiovascular Diseases...) :
At least in vitro,
insulin is a potent
inducer of
PAI-1 synthesis by human hepatic cells, and, we have recently disentangled the molecular mechanisms responsible for enhanced PAI-1 gene expression by insulin
Kietzmann et al., Blood 2003
(Anoxia) :
The expression of the plasminogen activator inhibitor-1 (
PAI-1 ) gene is
enhanced by
insulin both in vivo and in various cell types ... Mutation of the hypoxia response elements ( HRE-1 and HRE-2 ) in rat PAI-1 promoter, which could bind hypoxia inducible factor-1 (HIF-1), abolished the
induction of
PAI-1 by
insulin and PKB ... Thus, the
insulin dependent activation of the
PAI-1 gene expression can be mediated via the PI3K/PKB pathway and the transcription factor HIF-1 binding to the HREs in the PAI-1 gene promoter
López-Alemany et al., Eur J Biochem 2003
:
By using specific PAI-1 mutants with either VN binding or plasminogen activator (PA) inhibiting activities ablated, we have shown that the
PAI-1 mediated interference with
insulin signaling occurs through its direct interaction with VN, and not through its PA neutralizing activity
Bodary et al., Med Sci Sports Exerc 2003
(Obesity) :
In addition, modest decreases in
insulin and triglyceride in individuals with elevated body fatness do not
result in changes in
PAI-1 after short-term training
Venugopal et al., Proc Natl Acad Sci U S A 2004
(Insulin Resistance) :
Insulin induced
PAI-1 gene expression is up-regulated by a specific inhibitor of PI3K
McCarty et al., Med Hypotheses 2005
(Metabolic Syndrome X) :
Alternatively, hyperinsulinemia and hypertriglyceridemia have been suggested as mediators of PAI-1 excess in insulin resistance, inasmuch as
insulin and VLDL can
stimulate PAI-1 production in cell cultures
Pandey et al., FASEB J 2005
:
Finally, we demonstrate that the PKC pathway is also central for
PAI-1 induction in
response to
insulin and transforming growth factor-beta ( TGF-beta ), two additional molecules which are elevated in obesity and shown to directly induce PAI-1 in the adipocyte
Pandolfi et al., Arterioscler Thromb Vasc Biol 2005
(Atherosclerosis...) :
We determined
insulin effect on nitric oxide ( NO ) production and plasminogen activator inhibitor
(PAI)-1 synthesis in 12 fibroblast strains obtained from skin biopsy samples of 6 insulin-sensitive (IS) ( clamp M > 7 mg/kg body weight per minute ) and 6 insulin-resistant (IR) ( clamp M < 5 mg/kg body weight per minute ) healthy volunteers
Vuorinen-Markkola et al., Thromb Haemost 1992
(Coronary Thrombosis...) :
To directly examine the
effect of
insulin on
PAI-1 activity in vivo, we determined the response of PAI-1 activity in 17 normal subjects to acute hyperinsulinemia ( serum free insulin 92 +/- 8 mU/l ) during maintenance of normoglycemia ( plasma glucose 5.1 +/- 0.1 mmol/l )
Mukai et al., Am J Physiol Heart Circ Physiol 2007
:
Similarly, overexpression of a dominant negative mutant of PI3K or Akt increased TNF-alpha- and
insulin induced
PAI-1 expression ... The
induction of
PAI-1 by TNF-alpha and
insulin is mediated, in part, by ERK and p38 MAPK ... Simvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, which is known to activate PI3K/Akt, blocks TNF-alpha- and
insulin induced
PAI-1 expression ... Treatment with PI3K inhibitors reversed the inhibitor effects of simvastatin on TNF-alpha- and
insulin induced
PAI-1 expression
Yang et al., Acta Biochim Biophys Sin (Shanghai) 2007
:
Using human vascular endothelial cells ( ECV304 ) as the target, we studied the effect of caveolin (CAV)-1 in the course of
insulin stimulated expression of plasminogen activator inhibitor
(PAI)-1
Dimova et al., Ann N Y Acad Sci 2006
(Carcinoma, Hepatocellular...) :
The MAPK pathway and HIF-1 are involved in the
induction of the human
PAI-1 gene expression by
insulin in the human hepatoma cell line HepG2 ... The expression of the
PAI-1 gene is
increased by
insulin in different cells, although, the molecular mechanisms behind insulin induced PAI-1 expression are not fully known yet ... Here, we show that
insulin upregulates human
PAI-1 gene expression and promoter activity in HepG2 cells and that mutation of the hypoxia-responsive element ( HRE ) -binding hypoxia-inducible factor-1 (HIF-1) abolished the insulin effects ... Mutation of E-boxes E4 and E5 abolished the
insulin dependent activation of the
PAI-1 promoter only under normoxia, but did not affect it under hypoxia ... Furthermore, mutation of a putative FoxO1 binding site which was supposed to be involved in
insulin dependent
PAI-1 gene expression influenced the insulin dependent activation only under normoxia ... Thus,
insulin dependent
PAI-1 gene expression might be regulated by the action of both HIF-1 and FoxO1 transcription factors
Sato et al., Coron Artery Dis 2008
(Carcinoma, Hepatocellular...) :
Insulin ( 0.001-10 micromol/l )
increased accumulation of
PAI-1 protein in the conditioned media and PAI-1 mRNA expression in HepG2 cells ... A transient transfection assay of the human PAI-1 promoter-luciferase construct demonstrated that
insulin increased
PAI-1 promoter activity ... Simvastatin ( 10 micromol/l ), known to translocate membrane bound sterol regulatory element binding protein to nuclei, attenuated
PAI-1 mRNA expression
induced by
insulin ...
Insulin mediated augmented expression of
PAI-1 may be amenable to suppression attributable to pleiotropic effects of statins, potentially diminishing cardiovascular risk in patients with insulin resistance
Okazaki et al., Endocr J 2008
(Inflammation...) :
Interleukin 1beta and
insulin also cooperatively
increased the endogenous mRNA level of
PAI-1
Dimova et al., Thromb Haemost 2008
(Metabolic Diseases) :
Especially a defective
insulin response in the liver contributes to the development of hyperglycemia, dyslipidemia and peripheral insulin resistance and may
contribute to hepatic over-expression of
PAI-1 in diabetes type 2
Juhan-Vague et al., Diabete Metab 1991
(Coronary Disease...) :
Although in vitro
insulin stimulates the
PAI-1 synthesis in hepatocyte, but not in endothelial cells, acute elevation of insulinaemia in vivo in man does not result in an increase in PAI-1 levels
Jung et al., Biochem Biophys Res Commun 2009
(Hyperinsulinism) :
Insulin increases the expression of
PAI-1 , and inactivates the forkhead box containing protein FoxO1 ... Here, we examined whether adenoviral mediated expression of a constitutively active form of FoxO1 ( Ad-CA-FoxO1 ) inhibited
insulin stimulated
PAI-1 expression in human HepG2 hepatocellular liver carcinoma cells and mouse AML12 hepatocytes
Singh et al., Biochem Biophys Res Commun 2010
(Atherosclerosis...) :
The leptin dependent upregulation of PAI-1 mRNA and protein was comparable to
insulin induced
PAI-1 expression
Zhou et al., International journal of ophthalmology 2010
:
The corresponding gene expression and function can affect POAG progress, including
roles of
SERPINE1 in extracellular matrix, ENPP1 in
insulin inhibition, IL-6 in endogenous neuroprotection, IL-6, IL-6R and E-Sel in autoimmune response, LIPC and FGB in blood hyperviscosity syndrome, ADIPOQ in NOS/NO production, PON1 in vascular endothelial protection
Juhan-Vague et al., Thromb Haemost 1989
(Coronary Disease...) :
These results are in agreement with our previous report showing an in vitro
effect of
insulin on the synthesis of
PAI by a hepatocellular cell line
Kooistra et al., Thromb Haemost 1989
:
Plasminogen activator inhibitor 1 : biosynthesis and mRNA level are
increased by
insulin in cultured human hepatocytes ... To investigate a possible involvement of hepatocytes we have studied the
effect of
insulin on
PAI-1 production by primary cultures of human hepatocytes ... In all cases, however, the relative extent, time profile and dose-dependency of the
insulin induced increase in
PAI-1 synthesis were consistent ... Up to about 7 nM,
insulin dose-dependently
increased both
PAI-1 activity and PAI-1 antigen production
Alessi et al., Thromb Haemost 1988
(Liver Neoplasms, Experimental) :
Insulin induced a dose dependent increase of the
PAI-1 secretion by Hep G2 cell line
Chomiki et al., Thromb Haemost 1994
(Arteriosclerosis) :
The link observed between increased PAI-1 levels and insulin resistance has lead workers to investigate the
effects of
insulin or triglyceride rich lipoproteins on
PAI-1 production by cultured hepatocytes or endothelial cells
Seljeflot et al., Scand J Clin Lab Invest 1994
(Coronary Disease) :
The postulated regulating
role of
insulin for the steady state levels of
PAI-1 could probably not be elucidated in the present dynamic model
Klassen et al., Coron Artery Dis 1993
:
To determine whether the increased
PAI-1 , known to be associated with accelerated coronary artery disease in non-diabetic subjects, is a
consequence of direct effects of
insulin on endothelial cells, we performed the present study with primary cultures of human aortic endothelial cells ... Insulin at pharmacologic concentrations did not alter either PAI-1 or t-PA production by the human aortic endothelial cells, although
insulin stimulated
PAI-1 synthesis in human hepatoma ( Hep G2 ) cells as expected
McGill et al., Diabetes 1994
(Diabetes Mellitus...) :
These results are consistent with our previous observations demonstrating direct stimulatory
effects of
insulin and its precursors on cellular expression of
PAI-1 in vitro and observations by others demonstrating decreased basal fibrinolytic activity in NIDDM patients
Anfosso et al., J Clin Invest 1993
(Carcinoma, Hepatocellular...) :
The hepatoma cell line Hep G2 has been shown to synthesize
PAI-1 in
response to
insulin ... In contrast, the drug ( 10 ( -4 ) M ) inhibited
insulin mediated
PAI-1 synthesis ... The results indicate that
PAI-1 synthesis in
presence of
insulin is markedly increased in down-regulated cells, and that metformin inhibits this effect by acting at the cellular level
Ho et al., Thromb Res 1993
(Diabetes Mellitus) :
PAI activity was not
affected by the increase of plasma
insulin , cholesterol, TG or glucose
Petersen et al., Metabolism 1996
(Arteriosclerosis) :
These findings suggest that neither proinsulin nor
insulin regulate plasma levels of
PAI-1 and t-PA in young healthy women regardless of OC use status
Samad et al., Mol Med 1996
(Obesity) :
Insulin did not
increase PAI-1 in large vessel endothelial or smooth muscle cells ... Our results suggest that elevated PAI-1 associated with obesity may result in part from
insulin induced induction of
PAI-1 specifically by adipocytes within the fat itself
Pandolfi et al., Diabetologia 1996
:
Vascular smooth muscle cells ( vSMC ) play an important role in the development of atherosclerotic lesions ; however, the
role of
insulin and glucose in regulating
PAI-1 and t-PA production in vSMC is presently not known
Schneider et al., Coron Artery Dis 1996
(Arteriosclerosis...) :
Insulin can stimulate expression of PAI-1 in vitro, but infusions of insulin in human subjects have not
increased PAI-1 in blood in acute, euglycemic clamp studies
Nordt et al., Circulation 1997
:
Gemfibrozil attenuated the augmentation of synthesis and secretion of
PAI-1 induced by
insulin and its precursors directly and specifically
Samad et al., Ann N Y Acad Sci 1997
(Aneurysm...) :
Since both TNF-alpha and insulin are known to increase in obesity, the elevated levels of
PAI-1 observed in the plasma of obese individuals may
result from TNF-alpha and/or
insulin induction of PAI-1 in the adipose tissue itself
Schneider et al., Circulation 1997
(Arteriosclerosis) :
To determine whether arterial expression of
PAI-1 in
response to
insulin contributes to the increased PAI-1 observed, human and porcine arteries in culture were exposed to insulin, and results were compared with responses of specific arterial cellular constituents maintained in culture and coculture ...
Insulin increased accumulation of
PAI-1 in conditioned medium from arterial segments ( ng PAI-1 [ 1 nmol/L insulin minus control ] : human arteries 47+/-17, porcine arteries 3.1+/-1.2, P < .05 for each ) and from endothelial cells ( ECs ) cocultured with smooth muscle cells ( SMCs, ng PAI-1 [ 1 nmol/L insulin minus control ] : human cells 43+/-8, porcine cells 0.5+/-0.1, P < .05 for each )
Calles-Escandon et al., Diabetes 1998
(Diabetes Mellitus, Type 2...) :
We hypothesized that induction of increased
insulin accompanied by increased glucose and triglycerides would
increase PAI-1
Sobel et al., Circulation 1998
(Arteriosclerosis...) :
Because we have shown that
insulin can
stimulate PAI-1 synthesis in vivo and because accelerated vascular disease is common in such patients as well, we hypothesized that increased PAI-1, potentially predisposing to thrombosis, acute occlusion, and accelerating atherosclerosis because of thrombus associated mitogens, would be present in excess in atheroma from type 2 diabetic subjects