October 2015

  1. IGF: the Muscle, Bone and Nerve Promoter

    Structural (PyMOL) model of IGF-1. "Protein IGF1 PDB 1bqt" by Emw - Own work. Licensed under CC BY-SA 3.0 via Commons -

    Insulin-like growth factor 1 (IGF-1) is a hormone related to growth and development in animals. As the name suggests, it is closely related to insulin in terms of structure. IGF-1 binds to its own receptor, IGFR. Reductions in, or antagonism of, IGF-1 activity is associated with the wastage of organs associated with starvation and some forms of cancer1. IGF-1 and Muscle Growth IGF-1, signaling through calcineurin, may have a role in the regulation of growth in muscle tissue2. The expression of genes for these proteins (IGF-1 and CnAα) was found consistently in a study using duck embryos, focusing on the development of leg and breast muscle. This gene expression varied significantly over time, although it was at its highest at day 13 of embryonic development2. The expression of IGF-1 and CnAα was related to type IIb fibers, but not type I or type IIa fibers2. Another similar study reported that variations in the pectoralis muscles of duck chick mirrored those of MSTN (the gene for myostatin, another regulator of muscle development) and IGF-1 expression3. This indicates that IGF-1 is involved in the timing of muscle development in infant animals, and of that of the transition between muscle fiber types3. IGF-1 and Bone Growth  IGF-1 is also associated with the promotion of bone cell subtype (osteoclasts) proliferation. Reductions in the activity and populations of these cells are implicated in diseases that destroy bone, which include some forms of multiple myeloma4. The hormone may be used to confirm the osteoclastogenesis of proposed treatments such as glycosphingolipids in animal models of myeloma4. IGF-1 and Neuropathic Conditions IGF-1 is also known to be neurotrophic, or to influence the survival, function and development of neurons in the central nervous system5. This implies a role for this hormone in improved outcomes for animals with conditions that involve damage or death in these cells. Amyotrophic lateral sclerosis (ALS) is an example of these, in which motor neurons are affected, with an additional component of localized inflammation5. A study incorporating a mouse model of ALS found that the immunization of mice with a myelin-derived vaccine resulted in increases of IGF-1 in spinal tissue5. This led to reduced disease activity and increased survival in these animals5.      References: 1. Kwon Y, Song W, Droujinine IA, Hu Y, Asara JM, Perrimon N. Systemic organ wasting induced by localized expression of the secreted insulin/IGF antagonist ImpL2. Dev Cell. 2015;33(1):36-46. 2. Shu J, Li H, Shan Y, et al. Expression profile of IGF-I-calcineurin-NFATc3-dependent pathway genes in skeletal muscle during early development between duck breeds differing in growth rates. Dev Genes Evol. 2015;225(3):139-148. 3. Hu Y, Liu H, Shan Y, et al. The relative expression levels of insulin-like growth factor 1 and myostatin mRNA in the asynchronous development of skeletal muscle in ducks during early development. Gene. 2015;567(2):235-243. 4. Ersek A, Xu K, Antonopoulos A, et al. Glycosphingolipid synthesis inhibition limits osteoclast activation and myeloma bone disease. J Clin Invest. 2015;125(6):2279-2292. 5. Kunis G, Baruch K, Miller O, Schwartz M. Immunization with a Myelin-Derived Antigen Activates the Brain's Choroid Plexus for Recruitment of Immunoregulatory Cells to the CNS and Attenuates Disease Progression in a Mouse Model of ALS. J Neurosci. 2015;35(16):6381-6393.
  2. Ipamorelin: One GHS analog with many differences

    Ipamorelin.

    Ipamorelin. "Ipamorelin" by Ed (Edgar181) - Own work. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:Ipamorelin.

    Ipamorelin is a synthetic peptide that binds selectively to the growth hormone secretagogue receptor (GHS-R). It contains the artificial amino acids 2-aminoisobutyric acid (i.e. 2-methylalanine or Aib) and 2-naphthylalanine (2-Nal)1. These differentiate it from the peptide growth hormone releasing protein-1 (GHRP-1), on which it was based1. It has been found to have an efficacy and potency in releasing growth hormone comparable to that of GHRP-6 in in vitro and animal trials1. Ipamorelin was found to have lower potency, but higher efficacy, that GHRP-2 in a swine pharmacokinetic study1. Unlike the peptides GHRP-2 and -6, ipamorelin appears not to be associated with the release of adrenocorticotropic hormone (ACTH) or cortisol1. Appetite and the Gastrointestinal System Ipamorelin is known as a ghrelin mimetic. Like this natural molecule, it increases appetite and gut motility2. A study incorporating a rat model of postoperative decreases in these found that repeated 0.01-1mg/kg doses of ipamorelin significantly increased food intake, fecal output and body weight in the first 48 hours after an experimental surgery2. Ipamorelin and Diabetes Ghrelin has been found to elicit significant increases in the pancreatic insulin production of both normal and diabetic rats3. Therefore, ipamorelin may have similar effects. A study induced diabetes (via strepozocin administration) in rats. Pancreatic tissue samples were then taken from diabetic and control rats and incubated with a range of ipamorelin doses. This resulted in a moderately significant increase in the insulin secretion from the preparations taken from both groups of rats4. Ipamorelin-associated insulin release was successfully inhibited by drugs that block alpha- and beta-adrenergic receptors and calcium channels in both 'normal' and 'diabetic' samples4. This implies the mechanism by which ipamorelin stimulates the release of insulin4. Interestingly, alpha-adrenergic and calcium channel blockers fail to inhibit insulin release stimulated by ghrelin in diabetic rats3. Ipamorelin-mediated insulin release was also significantly blocked by atropine, an acetylcholine receptor antagonist4. Ipamorelin and Interactions  Growth hormone has been found to counteract the negative effects of repeated steroid treatments on nitrogen balance in the body5. These effects may lead to increased risks of liver damage. A rat study found that ipamorelin significantly reduced prednisolone-mediated urea synthesis, although to a lesser extent than growth hormone5. References: 1. Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-561. 2. Venkova K, Mann W, Nelson R, Greenwood-Van Meerveld B. Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus. J Pharmacol Exp Ther. 2009;329(3):1110-1116. 3. Adeghate E, Ponery AS. Ghrelin stimulates insulin secretion from the pancreas of normal and diabetic rats. J Neuroendocrinol. 2002;14(7):555-560. 4. Adeghate E, Ponery AS. Mechanism of ipamorelin-evoked insulin release from the pancreas of normal and diabetic rats. Neuro Endocrinol Lett. 2004;25(6):403-406. 5. Aagaard NK, Grofte T, Greisen J, et al. Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats. Growth Horm IGF Res. 2009;19(5):426-431.

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