scholarly journals Insulin-Like Growth Factor-I Induces Arginase Activity inLeishmania amazonensisAmastigote-Infected Macrophages through a Cytokine-Independent Mechanism

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Celia Maria Vieira Vendrame ◽  
Marcia Dias Teixeira Carvalho ◽  
Andre Gustavo Tempone ◽  
Hiro Goto
Keyword(s):  
Growth Factor ◽  
Arginase Activity ◽  
Alternative Activation ◽  
Insulin Like Growth Factor ◽  
Cytokine Levels ◽  
Igf I ◽  
Phosphatidylcholine Liposome ◽  
Tissue Fluids ◽  
Primary Form ◽  
Stimulation Of

Leishmania (Leishmania) amazonensisexhibits peculiarities in its interactions with hosts. Because amastigotes are the primary form associated with the progression of infection, we studied the effect of insulin-like growth factor (IGF)-I on interactions betweenL. (L.) amazonensisamastigotes and macrophages. Upon stimulation of infected macrophages with IGF-I, we observed decreased nitric oxide production but increased arginase expression and activity, which lead to increased parasitism. However, stimulation of amastigote-infected macrophages with IGF-I did not result in altered cytokine levels compared to unstimulated controls. Because IGF-I is present in tissue fluids and also within macrophages, we examined the possible effect of this factor on phosphatidylserine (PS) exposure on amastigotes, seen previously in tissue-derived amastigotes leading to increased parasitism. Stimulation with IGF-I induced PS exposure on amastigotes but not on promastigotes. Using a PS-liposome instead of amastigotes, we observed that the PS-liposome but not the control phosphatidylcholine-liposome led to increased arginase activity in macrophages, and this process was not blocked by anti-TGF-βantibodies. Our results suggest that inL. (L.) amazonensisamastigote-infected macrophages, IGF-I induces arginase activity directly in amastigotes and in macrophages through the induction of PS exposure on amastigotes in the latter, which could lead to the alternative activation of macrophages through cytokine-independent mechanisms.

Insulin and growth hormone act synergistically to stimulate insulin-like growth factor-I production by cultured chicken hepatocytes

1991 ◽  
Vol 128 (3) ◽  
pp. 389-393 ◽  
Author(s):  
B. Houston ◽  
I. E. O'Neill
Keyword(s):  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Free Medium ◽  
In Vitro System ◽  
Factor I ◽  
Maximal Stimulation ◽  
Igf I ◽  
Growth Factor I ◽  
Stimulation Of

ABSTRACT Cultured chicken hepatocytes were used to investigate whether insulin and GH interact to regulate insulin-like growth factor-I (IGF-I) production in vitro. In the first set of experiments hepatocytes were preincubated for 6 h in hormone-free medium, and the effects of various combinations of insulin and GH on IGF-I production over the next 24 h were quantified by radioimmunoassay. Basal IGF-I production was 5·36 pg IGF-I/μg DNA and this was increased 1·31±0·13-fold (mean ± s.e.m.) by insulin, 1·90±0·24-fold by GH and 4·46±0·68-fold by a combination of insulin and GH. These results demonstrate that insulin and GH interact synergistically to stimulate IGF-I production in vitro. The synergism with GH occurred at physiological concentrations of insulin with half-maximal stimulation occurring at an insulin concentration of 6 ng/ml. In hepatocytes which had been exposed to insulin immediately before the start of the experiment, the presence of insulin was no longer required for maximal stimulation of IGF-I production by GH. This in-vitro system will facilitate the study of the molecular basis of the interaction between insulin and GH. Journal of Endocrinology (1991) 128, 389–393

Normal somatomedin-C/insulin-like growth factor I binding and action in cultured human fibroblasts from Turner syndrome

1983 ◽  
Vol 104 (4) ◽  
pp. 502-509 ◽  
Author(s):  
Ron G. Rosenfeld ◽  
Laura A. Dollar ◽  
Raymond L. Hintz ◽  
Cheryl Conover
Keyword(s):  
Growth Factor ◽  
Turner Syndrome ◽  
Thymidine Incorporation ◽  
Insulin Like Growth Factor ◽  
Cell Replication ◽  
Somatomedin C ◽  
Factor I ◽  
Igf I ◽  
And Control ◽  
Stimulation Of

Abstract. Growth retardation is a major manifestation of Turner syndrome (TS). Since plasma growth hormone and somatomedin-C/insulin-like growth factor I (SM-C/IGF-I) levels are generally normal, growth failure has been ascribed to peripheral defects in SM-C/IGF-I receptors or action. We have measured the binding of [125I]SM-C/IGF-I to cultured fibroblast monolayers derived from patients with Turner syndrome, and have evaluated SM-C/IGF-I stimulation of both [3H]thymidine incorporation and cell replication. When compared to fibroblasts from normal adults, newborns, and agematched children, no significant differences were observed in specific binding of [125I]SM-C/IGF-I to fibroblast monolayers, and displacement curves demonstrated similar receptor affinities for all groups. Similarly, equivalent SM-C/IGF-I stimulation of [3H]thymidine incorporation was seen in both Turner and control fibroblasts. In the absence of serum, SM-C/IGF-I, at a concentration of 10–25 ng/ml, stimulated thymidine incorporation 3.7–11.8-fold in Turner fibroblasts and 1.9–9.8-fold in control cells. In combination with 1.0% human hypopituitary serum (HHS), SM-C/IGF-I stimulated thymidine incorporation 20–70-fold in all cell lines. Cell replication in both TS and control cells was increased 90% by the combination of SM-C/IGF-I + 0.5% HHS, and 140% by SM-C/IGF-I + 0.5% HHS + dexamethasone. We conclude that TS fibroblasts have normal SM-C/IGF-I receptors and sensitivity, and are capable of enhanced DNA synthesis and replication following SM-C/IGF-I stimulation.

Recombinant growth hormone and insulin-like growth factor I do not alter gonadotrophin stimulation of the baboon testis in vivo

1994 ◽  
Vol 131 (4) ◽  
pp. 405-412 ◽  
Author(s):  
Bronwyn A Crawford ◽  
David J Handelsman
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Recombinant Growth Hormone ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Human Primate ◽  
Stimulation Of

Crawford BA, Handelsman DJ. Recombinant growth hormone and insulin-like growth factor I do not alter gonadotrophin stimulation of the baboon testis in vivo. Eur J Endocrinol 1994;131:405–12. ISSN 0804–4643 In vitro studies indicate a physiological role for insulin-like growth factor I (IGF-I) in paracrine regulation of testicular function and recent clinical studies suggest a potential role for growth hormone (GH) and/or IGF-I in the treatment of hypogonadotrophic states in males. This study aimed to examine the effects of pretreatment with recombinant human GH (rhGH) or rhIGF-I on the response to gonadotrophins of the non-human primate testis in vivo. Using a balanced Latin square design with repeated measures, six prepubertal male hamadryas baboons (Papio hamadryas hamadryas) were treated in a cross-over sequence for periods of 18 days with daily im injections of rhGH (0.4 IU·kg−1 · day−1), rhIGF-I (0.1 mg·kg−1 · day−1) or saline with a 2-week washout period between each treatment. A single im injection of hCG (1500 IU) increased serum testosterone (p = 0.0002) but neither rhGH nor rhIGF-I influenced the timing or magnitude of this response (p > 0.5). A single im dose of FSH (75 IU) stimulated immunoreactive inhibin (p = 0.01) but also was unaffected in magnitude or timing by pretreatment with rhGH or rhIGF-I (p> 0.2). Circulating IGF-I levels were increased independently by hCG (p = 0.01) and FSH (p < 0.0001) administration. These findings indicate that neither GH nor IGF-I pre-treatment enhance acute gonadal responses to gonadotrophin stimulation of the prepubertal non-human primate testis in vivo. These findings suggest that GH or IGF-I treatment of hypogonadotrophic men without somatotrophin deficiency is unlikely to be beneficial. David J Handelsman, Andrology Unit, Royal Prince Alfred Hospital, Departments of Medicine and Obstetrics and Gynaecology, University of Sydney, Sydney 2006, Australia

Effects of insulin-like growth factor-II on growth hormone release from human somatotrophinoma cells in vitro

1991 ◽  
Vol 129 (3) ◽  
pp. 447-451 ◽  
Author(s):  
P. E. Harris ◽  
M. Daniels ◽  
R. A. James ◽  
S. J. Turner ◽  
J. Dewar ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hormone Release ◽  
Insulin Like Growth Factor ◽  
Inhibitory Effects ◽  
Variable Effect ◽  
Gh Secretion ◽  
Factor Ii ◽  
Igf I ◽  
Stimulation Of

ABSTRACT Insulin-like growth factor-I (IGF-I) and IGF-II receptors have previously been demonstrated on membranes prepared from human somatotrophinomas. IGF-I has been shown to have a variable effect on GH secretion by these tumours in vitro. The effects of purified IGF-II on GH secretion have not been described. We have studied the direct actions of human recombinant IGF-II on GH release from eight somatotrophinomas cultured in vitro. Somatotrophinoma cells were cultured as monolayers at a density of 105 cells/0·5 ml. Treatment with IGF-II for 4 and 24 h resulted in discrete inhibitory effects on GH release from two tumours (tumour 5:4 h, IGF-II 0·5 nmol/l; tumour 2; 24 h, IGF-II 1 nmol/l). Treatment with IGF-II for 24 h resulted in significant inhibitory effects on GH release from one tumour over a range of concentrations tested (IGF-II 0·5–10 nmol/l). Addition of human GH-releasing factor (hGRF)(1–44) (20 nmol/l) for 4 and 24 h resulted in stimulation of GH release by five tumours. Two tumours demonstrated significant inhibitory effects of IGF-II on GRF-stimulated GH release (tumour 2: 24 h, IGF-II 1–5 nmol/l; tumour 3; 4 h, IGF-II 5 nmol/l; 24 h, IGF-II 0·5–50 nmol/l). These data emphasize the heterogeneity of somatotrophinomas in terms of their response to modulators of GH secretion. IGF-II does not appear to have a modulatory role on GH release by most somatotrophinomas. Journal of Endocrinology (1991) 129, 447–451

Insulin-like growth factor I stimulates apical sodium/hydrogen exchange in human proximal tubule cells

1997 ◽  
Vol 272 (4) ◽  
pp. F484-F490 ◽  
Author(s):  
D. W. Johnson ◽  
B. K. Brew ◽  
P. Poronnik ◽  
D. I. Cook ◽  
M. J. Field ◽  
...  
Keyword(s):  
Growth Factor ◽  
Proximal Tubule ◽  
Hydrogen Exchange ◽  
Insulin Like Growth Factor ◽  
Proximal Tubule Cells ◽  
Factor I ◽  
Sodium Hydrogen ◽  
Igf I ◽  
Tubule Cells ◽  
Stimulation Of

To determine whether insulin-like growth factor I (IGF-I) stimulated apical sodium/hydrogen exchange (NHE), confluent primary human proximal tubule cells (PTC) were incubated for 48 h in serum-free media in the presence or absence of 100 ng/ml IGF-I. Cells incubated in IGF-I demonstrated significant increases in thymidine incorporation (181.2 +/- 30.3% of control values; n = 12, P = 0.01) and in resting intracellular pH (pHi) (7.52 +/- 0.08 vs. 7.30 +/- 0.06; n = 20, P < 0.05), as determined by 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein quantitative microspectrofluorometry. Following intracellular acid loading, ethylisopropylamiloride (EIPA)-inhibitable H+ efflux and 22Na+ influx after 1 min were both significantly enhanced in IGF-I-treated cells compared with controls (8.78 +/- 1.69 vs. 3.03 +/- 0.72 mM/min and 3.47 +/- 0.49 vs. 1.55 +/- 0.35 nmol x mg protein(-1) x min(-1), respectively). 22Na+ uptake studies in PTC grown on permeable supports demonstrated preferential stimulation of apical vs. basolateral NHE. The 50% inhibitory concentrations (IC50) in IGF-I-treated and control cells for EIPA (0.5 and 1.1 microM, respectively) and for HOE-694 (4.0 and 10.0 microM, respectively) were also consistent with predominant activation of apical, rather than basolateral, NHE activity. Kinetic analysis revealed an increase in maximal transport velocity (Vmax, 15.50 +/- 1.50 vs. 7.26 +/- 3.07 mM/min; n = 10, P < 0.05), without a significant change in antiporter affinity for extracellular Na+. Incubation of PTC with 100 ng/ml IGF-I produced an acute, reversible, and EIPA-inhibitable pHi increase of 0.05 +/- 0.01 pH units (n = 5, P < 0.05). The results suggest that IGF-I may contribute to the metachronous stimulation of apical NHE and PTC growth observed in many physiological and pathological conditions involving the human kidney.

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