Expression of insulin-like growth factor-I (IGF-I) receptor gene in rat brain and liver during development and in regenerating adult rat liver

Epidermal growth factor (EGF) is a key regulator of cell survival and proliferation involved in the pathogenesis and progression of different types of cancer. The EGF receptor (EGFR) is activated by binding of the specific ligand but also by transactivation triggered by different growth factors including GH. Chronically, elevated GH levels have been associated with the progression of hepatocellular carcinoma. Considering EGF and GH involvement in cell proliferation and their signaling crosstalk, the objective of the present study was to analyze GH modulatory effects on EGF signaling in liver. For this purpose, GH receptor-knockout (GHR-KO) and GH-overexpressing transgenic mice were used. EGFR content was significantly decreased in GHR-KO mice. Consequently, EGF–induced phosphorylation of EGFR, AKT, ERK1/2, STAT3, and STAT5 was significantly decreased in these mice. In contrast, EGFR content as well as its basal tyrosine phosphorylation was increased in transgenic mice overexpressing GH. However, EGF stimulation caused similar levels of EGFR, AKT, and ERK1/2 phosphorylation in normal and transgenic mice, while EGF induction of STAT3 and STAT5 phosphorylation was inhibited in the transgenic mice. Desensitization of the STATs was related to decreased association of these proteins to the EGFR and increased association between STAT5 and the tyrosine phosphatase SH2-containing phosphatase-2. While GHR knockout is associated with diminished expression of the EGFR and a concomitant decrease in EGF signaling, GH overexpression results in EGFR overexpression with different effects depending on the signaling pathway analyzed: AKT and ERK1/2 pathways are induced by EGF, while STAT3 and STAT5 activation is heterologously desensitized.

show abstract

“…Moreover, IGF1 binding to hepatocytes is barely detectable (Barreca et al . 1992, Santos et al . 1994).…”

Section: Introductionmentioning

confidence: 99%

GH modulates hepatic epidermal growth factor signaling in the mouse

González

Díaz²,

Miquet³

et al. 2009

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…IGF-I binds weakly to isolated hepatocytes and intact liver, which may be in part due to the low level of hepatocyte IGF-I receptor expression (31,32). Confocal immunofluorescence microscopy shows surface association of IGFBP-3 on isolated primary hepatocytes (33).…”

Section: Discussionmentioning

confidence: 96%

Evidence of a Role for Insulin-Like Growth Factor Binding Protein (IGFBP)-3 in Metabolic Regulation

et al. 2010

View full text Add to dashboard Cite

IGF-binding protein (IGFBP)-3 is a metabolic regulator that has been shown to inhibit insulin-stimulated glucose uptake in murine models. This finding contrasts with epidemiological evidence of decreased serum IGFBP-3 in patients with type 2 diabetes. The purpose of this study was to clarify the role of IGFBP-3 in metabolism. Four-week-old male IGFBP-3(-/-) and control mice were subjected to a high-fat diet (HFD) for 12 wk. IGFBP-3(-/-) mice were heavier before the initiation of HFD and at the end of the study period. Resting metabolic rate was significantly decreased in knockout mice; however, respiratory exchange ratio was not significantly different. Fasting blood glucose and insulin levels were significantly elevated in IGFBP-3(-/-) mice. However, IGFBP-3(-/-) mice had relatively normal glucose tolerance because the relative glucose excursion over time was not different between the groups. During hyperinsulinemic clamps, IGFBP-3(-/-) mice had increased basal hepatic glucose production, but after insulin stimulation, no differences in hepatic glucose production were observed. A second cohort of older IGFBP-3(-/-) mice on HFD displayed unexpected evidence of hepatic steatosis. In summary, glucose tolerance and clamp testing indicate that IGFBP-3(-/-) mice preserve insulin sensitivity despite evidence of increased basal glucose turnover and hepatic steatosis. We provide evidence that genetic deletion of IGFBP-3 modulates hepatic carbohydrate and lipid metabolism.

show abstract

“…Changes in the rate of translation have been reported in other biological systems. Discrepancies might also be due to alterations at the posttranslational [21] level, or may be caused by a different half-life of protein in the fetus.…”

Section: Discussionmentioning

confidence: 96%

Effects of triiodothyronine and bovine growth hormone on glucose transporter isoform-2 (GLUT-2) and glucokinase (GK) gene expression in pancreatic islets of fetal and adult rats

García-Flores

Blázquez

Zueco

2001

Pfl�gers Archiv European Journal of Physiology

View full text Add to dashboard Cite

This study was conducted to determine the effects of triiodothyronine (T3) and bovine growth hormone (bGH) on the expression of glucose transporter-2 (GLUT-2) and of glucokinase (GK) from pancreatic islets of fetal and adult rats. Incubation of both sets of pancreatic islets with T3 did not modify GLUT-2 mRNA levels, but did reduce the content of GLUT-2 protein, while it reduced the expression of GK mRNAs in fetal and adult pancreatic islets. Treatment of fetal and adult pancreatic islets with 1 microg/ml bGH did not alter the expression of GLUT-2 mRNAs, but significantly increased GLUT-2 protein levels in adult islets by 50%. Also, bGH had no effect on the GK mRNA content of fetal and adult pancreatic islets whereas, in contrast, there was a significant reduction in the amount of GK protein in fetal islets cultured with that hormone but not in those corresponding to adult rats. These findings suggest that T3 and bGH are able to modulate the expression of GLUT-2 and GK mRNAs and proteins in pancreatic islets in a manner different from that in the liver, as previously reported by others. In addition, both hormones produced different responses in fetal and in adult pancreatic islets.

show abstract

Expression of insulin-like growth factor-I (IGF-I) receptor gene in rat brain and liver during development and in regenerating adult rat liver

Cited by 23 publications

References 37 publications

GH modulates hepatic epidermal growth factor signaling in the mouse

GH modulates hepatic epidermal growth factor signaling in the mouse

Evidence of a Role for Insulin-Like Growth Factor Binding Protein (IGFBP)-3 in Metabolic Regulation

Effects of triiodothyronine and bovine growth hormone on glucose transporter isoform-2 (GLUT-2) and glucokinase (GK) gene expression in pancreatic islets of fetal and adult rats

Contact Info

Product

Resources

About