Direct demonstration of insulin-like growth factor-I-induced nitric oxide production by endothelial cells

Abstract

Several lines of evidence indicate that insulin-like growth factor-I (IGF-I) is a potent mediator of vasodilation. To elucidate the mechanism and site of action of IGF-I, we performed continuous monitoring of nitric oxide (NO) release from endothelial cells using a highly-sensitive amperometric NO-sensor. Two types of cultured cells were used: human umbilical vein endothelial cells and immortalized rat renal interlobar artery endothelial cells. In separate experiments, [Ca2+]i changes in response to IGF-I were measured spectrofluorometrically in fura-2-loaded cells. Stimulation with IGF-I resulted in a rapid, dose-dependent increase in [NO] as detected by the NO-probe positioned 1 mm above the monolayers, followed by a sustained elevation lasting for at least five minutes. The effect of IGF-I was significantly suppressed by pretreatment with anti-IGF-I antibody, suggesting that it was specific for IGF-I. NG-nitro-L-arginine methyl ester, an inhibitor of NO synthesis, significantly blunted responses to IGF-I, but dexamethasone preincubation did not reduce the IGF-I-induced release of NO. These results indicate that the observed IGF-I-induced release of NO is a result of activation of the constitutive, rather than the inducible type of NO synthase in endothelial cells. Genistein, a tyrosine kinase inhibitor, resulted in a profound suppression of the IGF-I-induced release of NO. IGF-I did not affect [Ca2+]i in either type of cells. Therefore, IGF-I-induced NO production by both types of endothelial cells is mediated via a tyrosine kinase-dependent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal backfat depth in gestating sows has a greater influence on offspring growth and carcass lean yield than maternal feed allocation during gestation

“…IGF-1 can induce nitric oxide production in endothelial cells. Nitric oxide functions as an endogenous vasodilator (Tsukahara et al, 1994) resulting in higher blood flow to the placenta, thereby increasing nutrient availability to the foetus (Reynolds et al, 2010). Therefore, the fact that Restricted gilts with low IGF-1 concentrations gave birth to the lightest piglets (Amdi et al, 2013), may not simply be a result of restricted nutrient supply but also due to decreased blood flow across the placenta.…”

The PI3-K/Akt pathway: roles related to alterations in vasomotor responses in diabetic models

“…At the cellular level, there is growing evidence that for some agonists, such as acetylcholine, histamine, and bradykinin (Peach, 1985;Moncada et al, 1997;Kamata and Nakajima, 1998), a rise in intracellular Ca 2+ is necessary for NO production. In contrast, with other forms of stimuli, such as fluid shear stress (Kuchan and Frangos, 1994), estrogen (Caulin-Glaser et al, 1997), and insulin/IGF (Tsukahara et al, 1994), a rise in Ca 2+ is not required for NO production. Many stimuli [including insulin, vascular endothelial growth factor (VEGF), β-agonists, adrenomedullin and shear-stress signals] have been reported to regulate NO production by phosphlylation of eNOS, which facilitates association of the enzyme with calmodulin, thus reducing its inhibitory interaction with caveolin-1 (Dimmeler et al, 1999;Fulton et al, 1999, Zeng et al, 2000Luo et al, 2000;Nishimatu et al, 2001).…”

Insulin-like growth factor I is a comitogen for hepatocyte growth factor in a rat model of hepatocellular carcinoma

“…Similarly, IGF-I has been reported to cause nitric oxide-dependent vasodilation in vascular beds. 42 Hence, elevated autocrine/paracrine IGF-I activity may act as a local vasodilator in the compromised liver to increase liver function. Whatever the specific role of IGF-I within the normal liver of tumor-burdened animals, it is tempting to speculate that the tumor is also subject to elevated intrahepatic IGF-I levels and that it uses this IGF-I in the absence of autogenic IGF-I production.…”