Basal expression and insulin-mediated induction of PAI-1 mRNA in Hep G2 cells

Uncertainties in the theoretical prediction for the inclusiveB → X s γ decay rate are discussed. We emphasize that there is no operator product expansion for this process. Nonetheless, some nonperturbative effects involving a virtual cc loop are calculable using the operator product expansion. They give a contribution to the decay rate that involves the B meson matrix element of an infinite tower of operators. The higher dimension operators give effects that are only suppressed by powers of m b Λ QCD /m 2 c ∼ 0.6, but come with small coefficients.

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“…Similar work has been done by Grant, Morgan, Nussinov, and Peccei [20]. We thank them for discussing their results with us prior to publication.…”

Section: Acknowledgmentssupporting

confidence: 65%

“…(8) is a special case in that the B (v)|b Γ αβ g s G αβ b |B(v) matrix element is known from the B * − B mass splitting. The n = 1 matrix element vanishes by the equations of motion[20]. The n > 1 terms in Eq.…”

mentioning

confidence: 98%

Comment on nonperturbative effects in

1997

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“…Insulin has also been shown to affect t-PA and PAI-1 expression and secretion. This effect, however, has been clearly demonstrated on liver cells (HepG2) [25][26][27][28], while the role of insulin in modulating the fibrinolytic system in endothelial cells is still controversial [17,18,29]. These results lend support to the hypothesis that hepatocytes and, possibly, endothelial cells might be the source of elevated circulating PAI-1 levels in diabetes.…”

Section: Discussionmentioning

confidence: 65%

Glucose and insulin independently reduce the fibrinolytic potential of human vascular smooth muscle cells in culture

Pandolfi¹,

Iacoviello

Capani³

et al. 1996

Diabetologia

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Hyperglycaemia and hyperinsulinaemia have both been related to accelerated atherosclerosis in non-insulin-dependent diabetes mellitus (NIDDM). Plasma fibrinolytic potential is reduced in NIDDM and it is known that glucose and insulin can modulate plasminogen activator inhibitor (PAI-1) and tissue-plasminogen activator (t-PA) secretion and can therefore regulate local fibrinolysis. 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. Therefore, we cultured arterial vSMC explanted from human umbilical cords and exposed them to increasing concentrations of glucose (5, 12, 20, 27, 35 mmol/l) or insulin (0.1, 0.5, 1, 10 nmol/l) in a serum free medium. After 24 h, PAI-1 and t-PA antigens and activity were evaluated in the culture medium; in cells exposed to 20 mmol/l glucose and to 0.5 nmol/l insulin PAI-1 gene expression was also evaluated. An increase in PAI-1 antigen was observed at each glucose concentration (by 138, 169, 251 and 357% as compared to 5 mmol/l glucose) which was paralleled by an increase in PAI-1 activity. t-PA concentration was also increased by glucose but its activity was sharply reduced. An increase in PAI-1 antigen was detected at each insulin level (by 121, 128, 156 and 300% as compared to no insulin). PAI-1 activity was slightly increased at the lowest insulin concentrations but markedly increased by 10 nmol/l insulin. t-PA antigen was also increased by insulin; however, its activity was markedly reduced at each concentration. As compared to control cells, PAI-1 mRNA was increased by 2.5 and 2.0 fold by 20 mmol/l glucose and 0.5 nmol/l insulin, respectively. We conclude that in human vSMC both glucose and insulin can affect the fibrinolytic balance so as to reduce fibrinolytic potential. This might contribute to decreased local fibrinolysis and thereby might accelerate the atherothrombotic process in NIDDM subjects.

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“…It is difficult to distinguish the effects of insulin resistance from those of hyperinsulinaemia, hypertriglyceridaemia, male pattern obesity, high BMI, systolic hypertension, low HDL-cholesterol and glucose intolerance. In vitro cell stimulation experiments provide evidence to implicate insulin [39][40][41] very low density lipoproteins from hypertriglyceridaemic subjects [42] and high glucose levels [43][44] in the production of elevated PAI-1 levels. However, in vivo studies have failed to demonstrate an effect of hyperinsulinaemia [45][46][47][48] or hypertriglyceridaemia [45] on PAI-1 levels.…”

Section: Resultsmentioning

confidence: 97%

Promoter (4G/5G) plasminogen activator inhibitor-1 genotype in Pima Indians: relationship to plasminogen activator inhibitor-1 levels and features of the insulin resistance syndrome

et al. 1996

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Elevated plasminogen activator inhibitor-1 may contribute to vascular disease in diabetes mellitus. Pima Indians have a low incidence of cardiovascular disease despite having a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM) which in this population is not associated with elevated plasminogen activator inhibitor-1 activity. In Caucasians an insertion/deletion (4G/5G) polymorphism in the promoter region of the plasminogen activator inhibitor-1 gene that has been related to activity levels of its protein in plasma differentially binds repressor and enhancer elements. In 265 Pima Indians (133 diabetic, 132 non-diabetic, 129 male, 136 female, male, mean age 46.6, range 34-68 years) the promoter genotype frequencies were 23.0% for 4G/4G, 49.8% for 4G/5G and 27.2% for 5G/5G compared to 35.4%, 50.8% and 13.8% respectively, (chi 2 = 15.3, 2 df, p < 0.0005) previously reported in Caucasians with NIDDM. The mean plasma activity levels in the three genotypes in the Pima Indians were 18.2, 19.1 and 18.1 U/ml, respectively. Plasminogen activator inhibitor-1 activities correlated with plasma insulin (r = 0.38, p < 0.0001), body mass index (r = 0.24, p < 0.0001), and with triglyceride level (r = 0.12, p = 0.054) but there was no relationship between promotor genotype and activity. A steeper regression slope between plasminogen activator inhibitor-1 activity and triglycerides has been observed in Caucasians with the 4G/4G genotype as compared to Caucasians with the other genotypes. This was not found in the Pima population which may indicate a functional difference in this gene associated with reduced cardiovascular risk and may be involved in the lack of association of plasminogen activator inhibitor-1 levels with NIDDM in Pima Indians.

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Basal expression and insulin-mediated induction of PAI-1 mRNA in Hep G2 cells

Cited by 20 publications

References 24 publications

Comment on nonperturbative effects in

Comment on nonperturbative effects in

Glucose and insulin independently reduce the fibrinolytic potential of human vascular smooth muscle cells in culture

Promoter (4G/5G) plasminogen activator inhibitor-1 genotype in Pima Indians: relationship to plasminogen activator inhibitor-1 levels and features of the insulin resistance syndrome

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