INT34777

Context Info Confidence 0.80 First Reported 1983 Last Reported 2011 Negated 1 Speculated 0 Reported most in Body Documents 82 Total Number 82 Disease Relevance 42.68 Pain Relevance 8.62

signal transduction (IGF1) extracellular space (IGF1) extracellular region (IGF1)

Anatomy Link Frequency molar 4 plasma 3 thyroid 3 pituitary 3 hepatocyte 2 IGF1 (Homo sapiens)

Pain Link Frequency Relevance Heat cytokine 111 100.00 Cholecystokinin 54 100.00 chemokine 18 100.00 agonist 200 99.68 Fibrositis 106 99.52 Bioavailability 90 99.52 Dopamine 194 99.44 Somatostatin 247 99.00 Pain 154 98.68 Clonidine 30 98.06

Disease Link Frequency Relevance Heat Cancer 811 100.00 Prolactinoma 195 100.00 Carcinoid 6 100.00 Hypercalcemia 30 99.98 Acromegaly 491 99.88 Congenital Anomalies 96 99.86 Reprotox - General 3 24 99.84 Parathyroid Cancer 1 99.76 Syndrome 80 99.68 Chronic Renal Failure 47 99.02

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Another approach was described by De Ceuninck et al [55], who noted that disruption of IGF-1 binding to the inhibitory binding proteins via small molecules, resulting in the release of free IGF-1, restores the anabolic response of human chondrocytes.

Localization (release) of IGF-1 in chondrocytes

1) Confidence 0.80 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1456997 Disease Relevance 0.15 Pain Relevance 0.07

IGF-I receptor localized on sSMCs and their processes and colocalized with IGF-I.

Localization (localized) of IGF-I

2) Confidence 0.79 Published 1996 Journal Regul. Pept. Section Abstract Doc Link 8988513 Disease Relevance 0.22 Pain Relevance 0.07

In addition, growth hormone (GH) secretion and serum insulin-like growth factor (IGF)-I levels fall.

Localization (secretion) of IGF

3) Confidence 0.78 Published 2004 Journal Treat Endocrinol Section Abstract Doc Link 16026102 Disease Relevance 0.37 Pain Relevance 0.06

This suggested resistance of the liver and other somatomedin-C secreting tissues to GH.

Localization (secreting) of somatomedin-C in liver

4) Confidence 0.78 Published 1993 Journal J. Clin. Endocrinol. Metab. Section Abstract Doc Link 8421094 Disease Relevance 0.82 Pain Relevance 0.17

In severely short patients with normal GH response to provocative test, and additionally extremely low IGF-1 and/or IGFBP-3, an IGF-1 generation test can be helpful to confirm the diagnosis of IGFD.

Localization (response) of IGF-1

5) Confidence 0.75 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2724186 Disease Relevance 0.57 Pain Relevance 0.05

In severely short patients with normal GH response to provocative test, and additionally extremely low IGF-1 and/or IGFBP-3, an IGF-1 generation test can be helpful to confirm the diagnosis of IGFD.

Localization (response) of IGF-1

6) Confidence 0.75 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2724186 Disease Relevance 0.57 Pain Relevance 0.05

Otherwise, primary GHI or IGFD is due to congenital resistance to GH action with low or absent peripheral IGF-1.2 This syndrome, also known as Laron syndrome, was first described by Laron in the late 1960s as pituitary dwarfisms with high serum GH.2 It is a very rare syndrome resulting from genetic abnormality of GH receptor, mainly occurring in patients with high consanguinity.2,5

Neg (absent) Localization (absent) of IGF-1 in pituitary associated with laron syndrome and syndrome

7) Confidence 0.75 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2724186 Disease Relevance 0.77 Pain Relevance 0

These results suggest that amphid neurons are important for insulin/IGF-1 signaling and that ethosuximide may extend lifespan by disrupting this pathway.

Localization (important) of IGF-1 in amphid neurons associated with lifespan

8) Confidence 0.73 Published 2008 Journal PLoS Genetics Section Body Doc Link PMC2565500 Disease Relevance 0.87 Pain Relevance 0.04

Determination of IGFPB3, IGF-1, and GH Levels

Localization (Determination) of IGF

9) Confidence 0.73 Published 2010 Journal Protein J Section Body Doc Link PMC2951508 Disease Relevance 0 Pain Relevance 0

Human growth hormone and somatomedin C suppress the spontaneous release of growth hormone in unanesthetized rats.

Localization (release) of somatomedin C

10) Confidence 0.73 Published 1983 Journal Endocrinology Section Title Doc Link 6684547 Disease Relevance 0 Pain Relevance 0.13

[From research of non-suppressible serum insulin activity to the clinical application of recombinant insulin-like growth factor (rhIGF-I)].

Localization (application) of IGF-I

11) Confidence 0.73 Published 1995 Journal Schweiz Med Wochenschr Section Title Doc Link 7624742 Disease Relevance 0.08 Pain Relevance 0.10

She was given a treatment with lanreotide 60 mg every four weeks and her IGF-1 levels decreased (Table 1).

Localization (decreased) of IGF-1

12) Confidence 0.72 Published 2010 Journal J Med Case Reports Section Body Doc Link PMC2845144 Disease Relevance 0.93 Pain Relevance 0.23

The study showed an autocrine/paracrine mechanism of IGF-1 secretion, and the stimulative effect of IGF-1 on proteoglycan synthesis in bovine IVD.

Localization (secretion) of IGF-1

13) Confidence 0.72 Published 2006 Journal J Orthop Surg Section Body Doc Link PMC1636034 Disease Relevance 0.23 Pain Relevance 0

The results presented in this report showed the response to IGF-1 was less striking in 1%FBS, but a marked elevation in cell proliferation and the dose-dependent effect was found between the concentrations of 10–100 ?

Localization (response) of IGF-1

14) Confidence 0.72 Published 2006 Journal J Orthop Surg Section Body Doc Link PMC1636034 Disease Relevance 0.24 Pain Relevance 0

IGF-I localized primarily in synthetic smooth muscle cells (sSMCs) in both de novo and restenotic plaques.

Localization (localized) of IGF-I in plaques

15) Confidence 0.70 Published 1996 Journal Regul. Pept. Section Abstract Doc Link 8988513 Disease Relevance 0.24 Pain Relevance 0.08

In all the children IGF-I and IGFBP-3 secretion was measured in a single blood sample during in morning hours.

Localization (secretion) of IGF-I in blood

16) Confidence 0.69 Published 2010 Journal Thyroid Res Section Body Doc Link PMC2858102 Disease Relevance 0.05 Pain Relevance 0

As a matter of fact, a direct effect of thyroid function on IGF-I secretion was not fully confirmed in our study, as there were no significant differences in an increase of IGF-I secretion between the euthyroid children and those, who presented with hypothyroidism during rhGH administration.

Localization (secretion) of IGF-I in thyroid associated with thyroid disease

17) Confidence 0.69 Published 2010 Journal Thyroid Res Section Body Doc Link PMC2858102 Disease Relevance 0.78 Pain Relevance 0

Statistical analysis included comparison of thyroid function (FT4 and TSH concentrations), IGF-I secretion (as IGF-I SDS) and its bioavailability (expressed as IGF-I/IGFBP-3 molar ratio) in particular time points, before and during rhGH therapy.

Localization (secretion) of IGF-I in molar associated with bioavailability

18) Confidence 0.69 Published 2010 Journal Thyroid Res Section Body Doc Link PMC2858102 Disease Relevance 0 Pain Relevance 0.05

According to our observations, the therapy with rhGH led to a similar increase of IGF-I secretion and of its bioavailability in the patients with different forms of disorders of GH secretion and activity.

Localization (secretion) of IGF-I associated with bioavailability

19) Confidence 0.69 Published 2010 Journal Thyroid Res Section Body Doc Link PMC2858102 Disease Relevance 0 Pain Relevance 0.05

Similarly, Bona et al. [28] documented that in the patients with hypothyroidism - both congenital and caused by thyroiditis - L-T4 replacement led to physiological increase of IGF-I and IGFBP-3 secretion.

Localization (secretion) of IGF-I associated with thyroiditis and thyroid disease

20) Confidence 0.69 Published 2010 Journal Thyroid Res Section Body Doc Link PMC2858102 Disease Relevance 0.99 Pain Relevance 0

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