Insulin Regulates the Expression of the Insulin-Like Growth Factor Binding Protein 2 mRNA in Rat Hepatocytes

Böni-Schnetzler, Marianne; Schmid, Christoph; Mary, J. Laws; Zimmerli, B.; Meier, Peter J.; Zapf, J.; Schwander, J; Froesch, E. R.

doi:10.1210/mend-4-9-1320

Cited by 76 publications

(40 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the dominant regulator of IGFBP-2 mRNA levels in hepatocytes is considered to be insulin. When added to primary cultures of liver cells, insulin strongly decreases IGFBP-2 mRNA levels (Böni-Schnetzler et al 1990). This result was also confirmed in our hepatocyte cultures from hypothyroid rats.…”

Section: Discussionmentioning

confidence: 99%

Tri-iodothyronine increases insulin-like growth factor binding protein-2 expression in cultured hepatocytes from hypothyroid rats

Demori

Bottazzi²,

Fugassa³

1999

Journal of Endocrinology

View full text Add to dashboard Cite

Previous evidence suggests the existence of a thyroid hormone-IGF axis in the liver and changes in hepatic insulin-like growth factor binding protein (IGFBP) expression in rats with altered thyroid status have been previously reported.The aim of this study was to check if the higher IGFBP-2 mRNA levels observed in liver of hypothyroid rats could be due to a direct effect of thyroid hormone on the IGFBP-2 gene. In our experiments, cultured hepatocytes isolated from normal and hypothyroid adult rats were used. Northern blot analysis revealed barely detectable IGFBP-2 mRNA in normal rat hepatocytes, but easily detectable signal in hypothyroid rat cells. Therefore, the effect of tri-iodothyronine (T 3 ) was investigated using cultured hepatocytes from hypothyroid rats as an in vitro model.The IGFBP-2 message was increased in a dosedependent manner in hepatocytes cultured for 12-24 h in the presence of T 3 . A similar increase occurred in accumulation of IGFBP-2 in the culture medium, as measured by RIA. The effect of T 3 on IGFBP-2 transcript levels appeared to consist of enhanced gene transcription and was independent of ongoing protein synthesis, but it was completely abolished by the incubation of hepatocytes with insulin. The latter result confirmed the dominant role of insulin in regulating IGFBP-2 expression by cultured hepatocytes.In vivo experiments confirmed an increase in hepatic IGFBP-2 mRNA and serum IGFBP-2 levels in hypothyroid rats and demonstrated, in addition, a significant increase in these measures in T 3 -treated rats.Taken together, our in vitro and in vivo results support a role for a thyroid hormone-IGF axis in the liver and suggest that other factors, such as insulin, interact in vivo with thryoid hormone in regulating hepatic IGFBP-2 expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Tri-iodothyronine increases insulin-like growth factor binding protein-2 expression in cultured hepatocytes from hypothyroid rats

Demori

Bottazzi²,

Fugassa³

1999

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Therefore, behavioral and pharmaceutical interventions may affect IGF-I and its binding proteins differentially according to factors that influence both growth hormone and nutritional status, including insulin and body composition (20). Insulin may affect IGF-I levels and activity by contributing to growth hormone stimulation of IGF-I production (13) and by increasing IGF-I bioavailability through direct inhibition of IGFBP-1 and IGFBP-2 synthesis at the liver (24)(25)(26)(27)(28)(29)(30). Associations of body fat and insulin with cancer risk may be mediated through alterations of bioavailable levels of IGF-I.…”

Section: Introductionmentioning

confidence: 99%

Interactions between Insulin, Body Fat, and Insulin-Like Growth Factor Axis Proteins

Ahmed

Thomas

Schmitz³

2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Background: The etiology of hormonally related cancers, such as breast and colon, has been linked to hyperinsulinemia and insulin resistance, the insulin-like growth factor (IGF) axis, and obesity. Methods: Data from 57 women (ages 30-50 years) were used to observationally examine cross-sectional and longitudinal relations between body fat (from dual-energy X-ray absorptiometry), insulin, IGF-I, and IGF-binding proteins (IGFBP-1, IGFBP-2, and IGFBP-3). Results: At baseline, participants who had greater than median body fat and insulin levels, >39% and >4.5 microunits/mL, respectively, had 2.3-to 2.6-fold lower IGFBP-1 (P < 0.004) and 1.9-to 2.0-fold lower IGFBP-2 (P < 0.004) compared with other participants; IGF-I and IGFBP-3 levels did not differ by body fat or insulin levels. Over 39 weeks, a

show abstract

“…At present, the factors affecting IGFBP bioavailability are not completely understood. IGFBP-1, IGFBP-2, and IGFBP-3 mRNA expression can be regulated by various hormones and growth factors (12)(13)(14)(15)(16)(17). Additionally, IGFBP-1 and IGFBP-3 have been shown to undergo posttranslational modifications, such as phosphorylation and proteolytic processing, that result in altered bioactivity (18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Posttranslational regulation of insulin-like growth factor binding protein-4 in normal and transformed human fibroblasts. Insulin-like growth factor dependence and biological studies.

Conover¹,

Kiefer²,

Zapf³

1993

J. Clin. Invest.

170

View full text Add to dashboard Cite

Insulin-like growth factor binding protein4 (IGFBP4) is a 24-26-kD protein expressed by a variety of cell types in vivo and in vitro. Treatment of normal adult human fibroblasts with 10 nM insulin-like growth factor II (IGF-II) for 24 h resulted in an 85% decrease in endogenous IGFBP4, as assessed by Western ligand blot analysis of the conditioned medium. Incubation of human fibroblast-conditioned medium (HFCM) with IGF-II under cell-free conditions led to a similar loss of IGFBP4. This posttranslationally regulated decrease in IGFBP-4 appeared to be due to a protease in HFCM: (a) It could be prevented with specific protease inhibitors or incubation at 40C; (b) proteolysis of recombinant human (rh) IGFBP-4 required HFCM; (c) immunoblotting and radiolabeling confirmed cleavage of IGFBP4 into 18-and 14-kD IGFBP4 fragments. The protease was specific for IGFBP4, and was strictly dependent on IGFs for activation. IGF-II was the most effective of the natural and mutant IGFs tested, inducing complete hydrolysis of rhIGFBP4 at a molar ratio of 0.25:1 (IGF/IGFBP4). Simian virus 40-transformed adult human fibroblasts also expressed IGFBP4 and IGFBP4 protease, as well as an inhibitor of IGFBP4 proteolysis. In biological studies, intact rhIGFBP4 potently inhibited IGF-I-stimulated [3HIaminoisobutyric acid uptake, whereas proteolyzed rhIGFBP-4 had no inhibitory effect. In conclusion, these data provide evidence for a novel IGF-dependent IGFBP4-specific protease that modifies IGFBP4 structure and function, and indicate a preferential role for IGF-II in its activation. Posttranslational regulation of IGFBP4 may provide a means for cooperative control of local cell growth by IGF-I and IGF-II.

show abstract

Insulin Regulates the Expression of the Insulin-Like Growth Factor Binding Protein 2 mRNA in Rat Hepatocytes

Cited by 76 publications

References 37 publications

Tri-iodothyronine increases insulin-like growth factor binding protein-2 expression in cultured hepatocytes from hypothyroid rats

Tri-iodothyronine increases insulin-like growth factor binding protein-2 expression in cultured hepatocytes from hypothyroid rats

Interactions between Insulin, Body Fat, and Insulin-Like Growth Factor Axis Proteins

Posttranslational regulation of insulin-like growth factor binding protein-4 in normal and transformed human fibroblasts. Insulin-like growth factor dependence and biological studies.

Contact Info

Product

Resources

About