Insulin - A growth hormone

Endocrinology and Diabetes Research Unit, Schneider Children's Medical Center of Israel, WHO Collaborating Center for the Study of Diabetes in Youth, Sackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel.
Archives of Physiology and Biochemistry (Impact Factor: 1.76). 03/2008; 114(1):11-6. DOI: 10.1080/13813450801928356
Source: PubMed


Insulin is a peptide hormone with a high degree of homology with the insulin-like growth factor I (IGF-I). Its biological actions are interlaced with those of GH and IGF-I. The objective of this study is to review the growth promoting actions of insulin. The experimental evidence consists of the use of organ cultures of neonatal mice condilar cartilage insulin which stimulates the cartilage cell differentiation and maturation. Injection of insulin to hypohysectomized rats stimulated tibial growth. Clinical evidence is manifold. Babies with diabetes and hypoinsulinemia are short, whereas babies with hyperinsulinism are big. Children with idiopathic short stature have low insulin whereas obese children with hyperinsulinism are tall. Hypo-insulinized children with diabetes slow their growth until the insulin dose is optimized. It remains to be clarified whether insulin exerts its growth promoting actions via its own receptors, via the IGF-I receptors, or via a hybrid (insulin--IGF-I) receptor.

19 Reads
  • Source
    • "The traditional view is that the metabolic impacts of insulin are primarily achieved through the INSR, while IGFs promote mitogenic effects through the IGF1R. Yet, there is crosstalk between the ligands and receptors, and evidence indicates that insulin and IGFs can induce similar effects on metabolism and growth [11] [12] [13] [14]. Upon ligand binding, INSR and IGF1R are activated through tyrosine kinase-mediated autophosphorylation, thereby stimulating various downstream pathways, the two best-characterized being the PI3K/Akt/mTOR and the mitogen-activated protein kinase (MAPK) pathways, the latter of which involves Ras, Raf, MEK, and ERK signaling molecules. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal neoplasia differentially expressed (CRNDE) is a novel gene that is activated early in colorectal cancer but whose regulation and functions are unknown. CRNDE transcripts are recognized as long noncoding RNAs (lncRNAs), which potentially interact with chromatin-modifying complexes to regulate gene expression via epigenetic changes. Complex alternative splicing results in numerous transcripts from this gene, and we have identified novel transcripts containing a highly-conserved sequence within intron 4 ("gVC-In4"). In colorectal cancer cells, we demonstrate that treatment with insulin and insulin-like growth factors (IGF) repressed CRNDE nuclear transcripts, including those encompassing gVC-In4. These repressive effects were negated by use of inhibitors against either the PI3K/Akt/mTOR pathway or Raf/MAPK pathway, suggesting CRNDE is a downstream target of both signaling cascades. Expression array analyses revealed that siRNA-mediated knockdown of gVC-In4 transcripts affected the expression of many genes, which showed correlation with insulin/IGF signaling pathway components and responses, including glucose and lipid metabolism. Some of the genes are identical to those affected by insulin treatment in the same cell line. The results suggest that CRNDE expression promotes the metabolic changes by which cancer cells switch to aerobic glycolysis (Warburg effect). This is the first report of a lncRNA regulated by insulin/IGFs, and our findings indicate a role for CRNDE nuclear transcripts in regulating cellular metabolism which may correlate with their upregulation in colorectal cancer.
    Biochimica et Biophysica Acta 10/2013; 1843(2). DOI:10.1016/j.bbamcr.2013.10.016 · 4.66 Impact Factor
  • Source
    • "More recently, HCV core protein seems to increase the serine phosphorylation of insulin receptor substrate (IRS)-1 and to activate c-Jun N-terminal kinase signaling and the proteasome activator 28γ, all of which are associated with insulin resistance [28–30]. Such hyperinsulinemia from insulin resistance—by its action on hepatic stellate cells, extracellular matrix, endothelial cells or connective growth factors—not only can accelerate the progression of fibrosis [31, 32], but also can increase accumulation of free fatty acids in the liver, leading to activation of some kinases, such as protein kinase C delta, inhibitor kappa B kinase, JNK, or mammalian target of rapamycin (mTOR) that are known to promote carcinogenesis [33, 34]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related mortality worldwide. Although hepatitis B still remains the most common risk factor worldwide, chronic hepatitis C virus (HCV) infection is the driving force for the increased incidence of HCC especially in Western countries and Japan. In hepatitis B virus (HBV)-endemic areas, after successful vaccination programs against HBV, chronic HCV infection is now emerging as an important cause of chronic liver diseases. Unlike patients with chronic hepatitis B, those with chronic hepatitis C (CHC) develop HCC in the presence of established cirrhosis in most cases. However, a significant minority of CHC develops HCC in the absence of cirrhosis. Although HCV is a RNA virus with little potential for integrating its genetic material into host genome, various HCV proteins, including core, envelope, and nonstructural proteins, have oncogenic properties by inducing oxidative stress, disturbing cellular regulatory pathways associated with proliferation and apoptosis, and suppressing host immune responses. Overall, a combination of virus-specific, host genetic, environmental, and immune-related factors are likely to determine progression to HCC. Strategies aimed at eliminating the virus may provide opportunities for effective prevention of the development of HCC. Pegylated interferon plus ribavirin therapy appears to be effective at reducing the risk of HCC in patients who achieve sustained virologic responses. In summary, with the emerging importance of CHC, mechanisms of HCV-associated hepatocellular carcinogenesis should be clarified to provide insight into advanced therapeutic and preventive approaches, which eventually decrease the incidence and mortality of HCC.
    Journal of Gastroenterology 03/2013; 48(6). DOI:10.1007/s00535-013-0770-9 · 4.52 Impact Factor
  • Source

Show more