Insulin induces tyrosine dephosphorylation of a 92 kDa protein in suspended monocytes

Zoppini, Giacomo; Galante, P.; Zardini, M.; Muggeo, Michele

doi:10.1007/bf03350321

Cited by 3 publications

(1 citation statement)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The possibility that proteolytic enzymes could be IGFBP and tissue specific provides a potential mechanism of specific delivery of a fraction of circulating IGFs to certain target cells [10, 20]. Holly et al [21]have suggested that IGFBP-3 may serve as the main circulating carrier, forming a reservoir which can supply IGFs to the tissues. In the tissues, proteolysis of IGFBP-3 makes this IGF available to the target cell receptors.…”

Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor Binding Protein (IGFBP)-3-Bound IGF-I and IGFBP-3-Bound IGF-II in Growth Hormone Deficiency

Belgorosky

Rivarola²

1999

Horm Res Paediatr

View full text Add to dashboard Cite

In blood, circulating IGFs are bound to six high-affinity IGFBPs, which modulate IGF delivery to target cells. Serum IGFs and IGFBP-3, the main carrier of IGFs, are upregulated by GH. The functional role of serum IGFBP-3-bound IGFs is not well understood, but they constitute the main reservoir of IGFs in the circulation. We have used an equation derived from the law of mass action to estimate serum IGFBP-3-bound IGF-I and IGFBP-3-bound IGF-II, as well as serum free IGF-I and free IGF-II, in 129 control children and adolescents (48 girls and 81 boys) and in 13 patients with GHD. Levels of serum total IGF-I, total IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 were determined experimentally, while those of IGFBP-4, IGFBP-5 and IGFPB-6, as well as the 12 affinity constants of association of the two IGFs with the six IGFBPs, were taken from published values. A correction for in vivo proteolysis of serum IGFBP-3 was also considered. In controls, serum total IGF-I, total IGF-II, IGFBP-3, IGFBP-3-bound IGF-I, IGFBP-3-bound IGF-II and free IGF-I increased linearly with age, from less than 1 to 15 years, in the two sexes. The concentrations of serum free IGF-I and free IGF-II were approximately two orders of magnitude below published values, as well as below the affinity constant of association of IGF-I with the type-1 IGF receptor. Therefore, it is unlikely that these levels can interact with the receptor. In the 13 patients with GHD, mean (± SD) SDS of serum IGFBP-3-bound IGF-I was –2.89 ± 0.97. It was significantly lower than serum total IGF-I, free IGF-I or IGFBP-3 SDSs (–2.35 ± 0.83, –1.12 ± 0.78 and –2.55 ± 1.07, respectively, p = 0.0001). The mean SDS of serum total IGF-II, IGFBP-3-bound IGF-II and free IGF-II were –1.25 ± 0.68, –2.03 ± 0.87 and 0.59 ± 1.10, respectively, in GHD. In control subjects, 89.8 ± 4.47% of serum total IGF-I and 77.3 ± 9.4% of serum total IGF-II were bound to serum IGFBP-3. In patients with GHD, the mean serum IGFBP-3-bound IGF-I and IGFBP-3-bound IGF-II were 8.63 ± 8.53 and 19.1 ± 14.7% below the respective means of control subjects (p < 0.02). In conclusion, in GHD there was a relative change in the distribution of serum IGFs among IGFBPs, due to the combined effects of the decrease in both total IGF-I and IGFBP-3. As a result, serum IGFBP-3-bound IGF-I and IGFBP-3 bound IGF-II, the main reservoirs of serum IGFs, were severely affected. This suggests that the decrease in serum IGFPB-3-bound IGF-I and IGFBP-3-bound IGF-II might have a negative effect for growth promotion and other biological effects of IGF-I and IGF-II. Finally, the estimation of serum IGFBP-3-bound IGF-I, or the percentage of total IGF-I and IGF-II bound to IGFBP-3, might be useful markers in the diagnosis of GHD.

show abstract

Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor Binding Protein (IGFBP)-3-Bound IGF-I and IGFBP-3-Bound IGF-II in Growth Hormone Deficiency

Belgorosky

Rivarola²

1999

Horm Res Paediatr

View full text Add to dashboard Cite

show abstract

The Various Effects of Amiodarone on Thyroid Function

Bogazzi¹,

Bartalena²,

Gasperi³

et al. 2001

Thyroid

138

View full text Add to dashboard Cite

Amiodarone, a benzofuranic-derivative iodine-rich drug used mostly for tachyarrhythmias, often causes changes in the peripheral metabolism of thyroid hormones mainly due to the inhibition of 5'-deiodinase activity: an increase in serum thyroxine and reverse triiodothyronine, and a decrease in serum triiodothyronine concentrations. Overt thyroid dysfunction, either amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH), occurring in 14% to 18% of patients receiving long-term treatment, may develop both in apparently normal thyroid glands and in glands with preexisting abnormalities. AIH is mainly due to the failure to escape from the acute Wolff-Chaikoff effect, and, in patients with thyroid autoimmune phenomena, to concomitant Hashimoto's thyroiditis. AIT is due to excess iodine-induced thyroid hormone synthesis (type I AIT) or to amiodarone-related destructive thyroiditis (type II AIT), although mixed forms often occur. Treatment of AIH consists of levothyroxine replacement therapy while continuing amiodarone therapy; alternatively, amiodarone can be discontinued, if possible, and the natural course toward euthyroidism can be accelerated by a short trial of potassium perchlorate. In type I AIT, the simultaneous administration of thionamides and potassium perchlorate is the treatment of choice, while in type II AIT steroids are the most useful therapeutic option. Mixed forms are best treated with a combination of thionamides, potassium perchlorate, and glucocorticoids. The low thyroidal 131I uptake usually makes radioiodine therapy not feasible, while thyroidectomy is a valid alternative in cases resistant to medical therapy.

show abstract

Protein tyrosine phosphatases: their role in insulin action and potential as drug targets

Evans¹,

Jallal²

1999

Expert Opinion on Investigational Drugs

View full text Add to dashboard Cite

Protein tyrosine phosphatases (PTPases) are the enzymes responsible for the selective dephosphorylation of tyrosine residues. PTPases function to regulate a wide array of biological responses mediated by growth factors and other stimuli by balancing the cellular level of phosphotyrosine in concert with their counterparts, protein tyrosine kinases. The important roles which PTPases play in regulating intracellular signalling and, ultimately, biological function along with the recent availability of information regarding their structural features has highlighted them as potential targets for pharmacological modulation. This is demonstrated by the increased level of activity directed towards the identification of novel small-molecule PTPase inhibitors. The rationale and potential utility of this drug discovery approach is discussed here, with particular emphasis on its application for the treatment of insulin resistance and Type 2 diabetes.

show abstract

Insulin induces tyrosine dephosphorylation of a 92 kDa protein in suspended monocytes

Cited by 3 publications

References 26 publications

Insulin-Like Growth Factor Binding Protein (IGFBP)-3-Bound IGF-I and IGFBP-3-Bound IGF-II in Growth Hormone Deficiency

Insulin-Like Growth Factor Binding Protein (IGFBP)-3-Bound IGF-I and IGFBP-3-Bound IGF-II in Growth Hormone Deficiency

The Various Effects of Amiodarone on Thyroid Function

Protein tyrosine phosphatases: their role in insulin action and potential as drug targets

Contact Info

Product

Resources

About