Insulin like growth factor 1 increases vascular smooth muscle nitric oxide production

Muniyappa, Ranganath; Walsh, Mary F.; Rangi, J.S.; Zayas, Ricardo M.; Standley, Paul R.; Ram, Jeffrey L.; Sowers, James R.

doi:10.1016/s0024-3205(97)00594-8

Cited by 73 publications

(54 citation statements)

References 22 publications

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“…However, it is controversial whether excessive secretion of GH and IGF-1 and/or multiple risk factors associated with acromegaly contribute to the development of CVD. It has been shown that recombinant GH induces endothelial NO synthase expression and NO production in human endothelial cells [15], and that IGF-1 stimulates NO production in rat vascular smooth muscle cell [16] and diminishes vascular contractility [17]. These data strongly suggest that GH and IGF-1 have a direct and acute effect on vascular endothelial and smooth muscle cells to stimulate NO production.…”

Section: Discussionmentioning

confidence: 95%

Improvement of Endothelial Dysfunction in Acromegaly after Transsphenoidal Surgery

et al. 2008

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Abstract. Flow-mediated vasodilatation (FMD) is a vascular functional test to detect endothelial dysfunction at the early stage of cardiovascular diseases. Patients with active acromegaly have higher morbidity and mortality due to cardiovascular events. To determine whether active acromegaly is associated with endothelial dysfunction, we studied 17 patients with active acromegaly for measurements of FMD, carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV), and other biochemical parameters before and 3 months after transsphenoidal surgery (TSS). Baseline %FMD in patients with active acromegaly was significantly lower than that in age-and sex-matched control subjects. After TSS, the mean %FMD in acromegaly significantly increased from 5.3% to 7.4%; 12 patients had increased %FMD (responders), whereas 5 patients had decreased or unchanged %FMD (non-responders). However, neither carotid IMT nor baPWV changed after TSS. Serum levels of GH, insulin-like growth factor (IGF)-1, total cholesterol, lowdensity lipoprotein cholesterol (LDL-C), hemoglobin HA1C, fasting plasma glucose and insulin levels, and homeostasis model assessment (HOMA)-R significantly decreased, whereas high-density lipoprotein cholesterol significantly increased. Responders had significantly lower baseline %FMD than did non-responders and both insulin levels and HOMA-R significantly decreased in responders, but not in non-responders after TSS. Simple regression analysis revealed that the change of %FMD showed a significant negative correlation with that of LDL-C, but not of IGF-1 or GH, in responders. In conclusion, it is suggested that endothelial dysfunction associated with active acromegaly improves soon after TSS, which is related to LDL-C and/or insulin resistance, but not to excess GH and/or IGF-1 itself.

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Section: Discussionmentioning

confidence: 95%

Improvement of Endothelial Dysfunction in Acromegaly after Transsphenoidal Surgery

et al. 2008

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“…Samples were homogenized using a 25-gauge syringe and then boiled for 5 min. Protein samples (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) µg/lane) were separated by electrophoresis on 7.5% SDS-PAGE gels and then transferred to polyvinylidene difluoride transfer membranes. Membranes were blocked for 1 h with 3% BSA in Tris-buffered saline containing 0.05% (vol/vol) Tween 20 and 0.05% (vol/vol) NP-40 and then incubated for 1 h with anti-PKC isoform-specific monoclonal antibodies at a 1:1,000 (PKC-␣, -␤, -␥, and -) or 1:750 (PKC-␦, -⑀, -, -, -, and -µ) dilution.…”

Section: Methodsmentioning

confidence: 99%

Participation of PI3K and atypical PKC in Na⁺-K⁺-pump stimulation by IGF-I in VSMC

Sweeney

Wang

et al. 1999

American Journal of Physiology-Heart and Circulatory Physiology

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The activity of the Na+-K+-pump is intricately linked to the maintenance of vascular tone. Here we demonstrate that insulin-like growth factor I (IGF-I) increases Na+-K+-pump activity in the vascular smooth muscle cell (VSMC) clone A7r5 in a time- and dose-dependent manner. This stimulatory effect of IGF-I was prevented by the tyrosine kinase inhibitor genistein (5 μM) and by the specific phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin (100 nM) and LY-294002 (25 μM). IGF-I activated a wortmannin-sensitive PI3K and its purported effector, the atypical protein kinase C (PKC)-ζ. Stimulation of PKC-ζ was prevented by the generic PKC inhibitor GF109203x (bisindolylmaleimide, 10 μM). Downregulation of diacylglycerol-sensitive (conventional and novel) PKCs by 24-h pretreatment with 1 μM phorbol 12-myristate 13-acetate had no effect on IGF-I-stimulated Na+-K+-pump activity. Similarly, inhibition of only conventional and novel PKCs with GF109203x (1 μM) had no effect on IGF-I-stimulated Na+-K+-pump activity. In contrast, a concentration of GF109203x (10 μM) that also inhibits the atypical PKCs abolished Na+-K+-pump stimulation by IGF-I. Neither the Na+-K+-2Cl−cotransporter inhibitor bumetanide (100 μM) nor the Na+/H+exchanger inhibitor HOE-694 (5 μM) affected the Na+-K+-pump stimulation by IGF-I, suggesting that a rise in intracellular Na+ concentration is not necessary for increased Na+-K+-pump activity. These results suggest that IGF-I directly stimulates the Na+-K+pump via a signaling pathway involving PI3K and atypical PKC (ζ).

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“…It has been shown that IGF-I stimulates NO production in an age-related manner, which in turn may mediate IGF-I-induced attenuation of vascular contractility (Walsh et al 1996, Muniyappa et al 1997, Ren et al 1999. Early studies indicated that down-regulation or activation of protein kinase C (PKC) by phorbol myristate acetate (PMA) affects the IGF-I-induced DNA synthesis in SMCs (Dempsey et al 1990, Pukac et al 1998, suggesting that PKC activation is required for IGF actions.…”

Section: The Multiple and Redundant Intracellular Igf Signaling Pathwmentioning

confidence: 99%

Specifying the cellular responses to IGF signals: roles of IGF-binding proteins

Duan

2002

Journal of Endocrinology

128

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Regulation of peptide growth factor/hormone activities by secreted hormone-binding proteins has emerged as a common theme in cell-cell signaling. Among the beststudied examples are members of the IGF-binding protein (IGFBP) gene family. These secreted proteins bind the IGF ligands with equal or even greater affinities than do the IGF receptors, and therefore are placed in a critical regulatory position between IGFs and their cell surface receptors. The circulating IGF/IGFBP complexes prolong the half-lives of IGFs and buffer the potential hypoglycemic effects of IGFs. Locally expressed IGFBPs provide a means of localizing IGFs in specific cells and can alter the IGF biological activity. While some members of the IGFBP gene family have been consistently shown to inhibit IGF actions by preventing them from gaining access to the IGF receptors, others potentiate IGF actions by facilitating the ligand-receptor interaction. Furthermore, recent studies indicate that some IGFBPs can regulate several cellular processes through ligandindependent mechanisms. This review will focus on the roles of IGFBPs in vascular smooth muscle cells. A conceptual model of the molecular mechanisms by which IGFBPs act to determine the specific physiological outcomes of IGF stimulation is proposed and discussed.

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Insulin like growth factor 1 increases vascular smooth muscle nitric oxide production

Cited by 73 publications

References 22 publications

Improvement of Endothelial Dysfunction in Acromegaly after Transsphenoidal Surgery

Improvement of Endothelial Dysfunction in Acromegaly after Transsphenoidal Surgery

Participation of PI3K and atypical PKC in Na⁺-K⁺-pump stimulation by IGF-I in VSMC

Specifying the cellular responses to IGF signals: roles of IGF-binding proteins

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Insulin like growth factor 1 increases vascular smooth muscle nitric oxide production

Cited by 73 publications

References 22 publications

Improvement of Endothelial Dysfunction in Acromegaly after Transsphenoidal Surgery

Improvement of Endothelial Dysfunction in Acromegaly after Transsphenoidal Surgery

Participation of PI3K and atypical PKC in Na+-K+-pump stimulation by IGF-I in VSMC

Specifying the cellular responses to IGF signals: roles of IGF-binding proteins

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Participation of PI3K and atypical PKC in Na⁺-K⁺-pump stimulation by IGF-I in VSMC