Abstract
Hepatocyte differentiation, proliferation, and apoptosis are affected by growth factors produced in liver. Insulin-like growth factor 1 and 2 (IGF1 and IGF2) act in response to growth hormone (GH). Other IGF family components include at least six binding proteins (IGFBP1 to 6), manifested by both IGFs develop due to interaction through the type 1 receptor (IGF1R). The data based on animal models and/or in vitro studies suggest the role of IGF system components in cellular aspects of hepatocarcinogenesis (cell cycle progression, uncontrolled proliferation, cell survival, migration, inhibition of apoptosis, protein synthesis and cell growth), and show that systemic IGF1 administration can reduce fibrosis and ameliorate general liver function. In epidemiologic and clinicopathological studies on chronic liver disease (CLD), lowered serum levels, decreased tissue expression of IGF1, elevated production of IGF1R and variable IGF2 expression has been noted, from the start of preneoplastic alterations up to the developed hepatocellular carcinoma (HCC) stage. These changes result in well-known clinical symptoms of IGF1 deficiency. This review summarized the current data of the complex role of IGF system components in the most common CLD (nonalcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma). Better recognition and understanding of this system can contribute to discovery of new and improved versions of current preventive and therapeutic actions in CLD.
Highlights
The liver is a key organ in insulin-mediated regulation of metabolism
IGF1 and IGF2 were named insulin-like growth factors because of their structural homology with insulin (~50% identical sequence) and similar metabolic actions
This review summarized the current data of the complex role of IGF system components in the most common chronic liver disease (CLD)
Summary
The liver is a key organ in insulin-mediated regulation of metabolism. In addition to its key role in whole-body, glucose and lipid homeostasis, this organ is a major site of the synthesis of plasma proteins and endocrine factors such as insulin-like growth factor 1 and 2 (IGF1 and IGF2), as well as their binding proteins (IGFBPs) and thereby influences whole-body metabolism and growth [1]. IGF1 plays a central role in pre- and postnatal growth in humans and other mammals, as a key mediator of the GH actions, while being involved in the control of intermediary metabolism, tissue repair and disease pathogenesis throughout life [13,14,15] Both IGFs are central hormones involved in metabolic signaling, affecting glucose uptake, lipogenesis, glycogen storage, and suppression of protein degradation [16,17]. Nonalcoholic fatty liver disease, defined as abnormal accumulation of triglycerides in the liver (i.e., >5%) in the absence of significant alcohol intake, is recognized as the most common cause and form of CLD, and is estimated to affect 30% of adults and 10% of children in the United States [28], with its worldwide prevalence continuously increasing, in correlation with the growing obesity epidemic [26,29,30] This form of CLD encompasses a spectrum of histologic findings, including uncomplicated steatosis, steatosis with inflammation and steatohepatitis (nonalcoholic steatohepatitis, NASH). Current epidemiologic studies confirm a correlation between the serum levels of IGF system components and the extent of hepatocellular function (see below)
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