Interactive effects of nutrients and hormones on the expression of insulin‐like growth factor binding protein‐1 (IGFBP‐1) mRNA and peptide, and IGF I release from isolated adult rat hepatocytes

Abstract

Isolated adult rat hepatocytes were used to investigate and compare the actions of glucose or amino acids and insulin, glucagon, growth hormone, and dexamethasone on the expression of insulin-like growth factor binding protein (IGFBP) mRNA, or the release of IGFBP and IGF peptides in vitro. Ligand blot analysis of culture medium conditioned for 24 h by monolayers of hepatocytes in the presence of 6.5 mM glucose revealed two species of IGFBPs, an abundant form of 30-32 kDa and a minor species of 22-24 kDa. Western blotting showed that two IGFBPs of 29-30 and 32 kDa were recognized by antiserum against hIGFBP-1, whereas hepatocytes contained a 1.6 kb transcript on Northern blot with a rat IGFBP-1 cDNA. Insulin-like growth factor BP-2 mRNA was not detected in hepatocytes and IGFBP-2 immunoreactive peptide not present in conditioned medium. The release of IGFBP-1, determined by ligand blot, was independent of glucose concentration over the range of 2.7 mM-11.1 mM, but IGFBP-1 mRNA was decreased following incubation with 6.5 mM glucose compared with 2.7 mM glucose. The release of IGFBP-1 by hepatocytes was inhibited by insulin (10 nM-1 microM), as was mRNA abundance. However, these effects of insulin on IGFBP-1 diminished with increasing glucose concentration. Increasing concentrations of total amino acids increased IGFBP-1 release as did dexamethasone (100 pM-100 nM), whereas growth hormone and glucagon were without effect. The release of IGF I was increased by insulin, growth hormone and dexamethasone but was decreased by glucagon and amino acids, whereas changes in glucose concentration had no effect. The results show that isolated adult rat hepatocytes release IGF I and IGFBP-1 under the interactive control of nutrients and hormones involved in metabolic homeostasis.

IGF-I production by adult rat hepatocytes is stimulated by transforming growth factor-alpha and transforming growth factor-beta1

“…IGF-I, IGFBP-1 and -4 messages were clearly expressed by rat hepatocytes cultured in basal medium while IGFBP-2 mRNA was not detected, in agreement with other authors (25). No effect was elicited by TGF-a or TGF-b 1 on IGF-I mRNA levels and on mRNAs encoding for IGFBP-1 and -4.…”

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

“…As shown in Fig. 1, Northern blot analysis revealed barely detectable IGFBP-2 mRNA in normal rat hepatocytes, according to Arany et al (1993). In contrast, when cells were prepared from PTU-treated hypothyroid rats, the IGFBP-2 message was readily detected.…”

Changes in bioactive IGF-I and IGF-binding protein-1 during an oral glucose tolerance test in patients with liver cirrhosis

“…Circulating IGF-I and IGFBP-1 are both synthesized predominantlyinthe liver under the control of various hormones (10)(11)(12)(13)(14), and accordingly,c hronicl iver disease has ap rofound impact on the plasma concentrations of IGF-I and IGFBP-1. Indeed, in comparison to healthysubjects, increasedcirculating levels of IGFBP-1, but lower total and free IGF-I, are characteristic features of liver cirrhosis (15)(16)(17)(18)(19).…”