Post on 11-Apr-2017
Insulin-Like Growth Factor-1 and the
BodyJahzelle Ambus, Delany Brown, Christi
Burshek, Preston Crenshaw, Jordan Drake
IGF-1 is a polypeptide hormone made up of seventy amino
acids Sourced from the liver. Similar in structure to the hormone insulin, from which it
gets its name It operates not just in an endocrine manner but is also
believed to operate in a paracrine and autocrine fashion as well.
Received by a transmembrane receptor similar in structure to an insulin receptor, but with a higher affinity for IGF-1.
Expression of IGF-1 gene is insulin dependent
The Hormone
Promotes hypoglycemia and controls carbohydrate
metabolism and glycogen synthesis Insulin like effect
Also thought to affect lipolysis, enabling use of free fatty acids Regulated in adipocytes by GH Suggested due to research on patients with GH insensitivity
syndrome Increase in muscle hypertrophy
causes an increase in protein synthesis a decrease in protein degradation Due to combined properties of GH and insulin
Promotes increase in collagen synthesis thought to control the actions of growth hormone May regulate myoblast differentiation via miRNAs
Function of IGF-1
The Role of IGF-1 in the
BodyGlycogen synthesis
Lipid oxidation
Protein synthesis
Protein degradation
Collagen synthesis
Guha et al. (2013)
1. IGF-1 binds to the receptor IGF-1R
2. this activates PI3K, which produces PIP3, which in turn activates Akt
3. Akt controls protein synthesis via mTOR pathway
4. Akt also blocks GSK3β, which would normally block protein synthesis
5. AKT blocks protein degradation by inactivating Fox0 transcription factors
This pathway is how IGF-1 leads to increased muscle mass.
How it Operates
Hitachi et al. (2014)
MiRNAs help regulate skeletal muscle by helping control gene expression
Help degrade mRNA Inhibit translationThese particular miRNAs target the IGF-1 pathway: MiRNA-128a: has potential to
increase muscle mass by acting as a negative regulator
MiRNA-486: plays a role in connecting sarcomeres to the sarcoplasm by producing Ank1.5, helps regulate Akt by targeting PTEN, decreases PTEN and Fox01
MiRNA-199a-3p: regulates myogenesis by targeting certain molecules in IGF-1 pathway
The Role of MicroRNAs
Hitachi et al. (2014), Jia et al, (2014)
The role of IGF-1 begins
after muscle have been broken down or damaged following exercise.
IGF-1 acts on satellite cells, which are centrally involved with muscle growth and repair.
IGF-1 and satellite cells colocalize after a bout of acute exercise. Grubb et. al (2014)
A study done by Fragala et. al (2014), suggests that IGF-1R on leukocytes facilitates muscle recovery.
Exercise and IGF-1
What types of exercise
influence this response? Resistance training Aerobic Anaerobic
Generally, the intensity of the exercise is more relevant to this process than the type.
Exercise and IGF-1
Adaptions to exercise
Neural adaptions Increased rate coding Increased motor recruitment Increase in neural drive
Uptake of IGF-1 by hippocampus stimulates neurogenesis. Pareja –Galeana et. al (2013)
Anatomical adaptions Hypertrophy
Increases protein synthesis Decreases protein
degradation
Exercise and IGF-1
IGF-1-Akt pathway
is essential for muscle growth.
Induces hypertrophy and blocks atrophy
Exercise & IGF-1
Greater risk for neural degeneration and related
diseases, such as Alzheimer's and Dementia; as well as seizers.
Increased susceptibility to fibromyalgia, high BMI, and fatigue, all of which contribute to a decreased ability to exercise.
Effect the central bodily systems and shows side effects such as increased fluid retention, hypoglycemia, lipohypertrophy, increase in liver and kidney size and function, and acromegaly
When Proper Function is impaired.
A Lack of the hormone can be seen by maleffects
throughout the body. Neural
Because IGF-1 plays a role in neural plasticity and increased neural regeneration, when it is lacking, neural degeneration can exceed the rate of regenerations. This leads to increased risk of major brain diseases.
In addition to its protagonistic role in the creation of neurons, it also aids in the clearance of amyloid beta (Aβ), a protein central in the Alzheimer’s disease.
Low IGF-1 Levels
Doi et. al. (2015)
Muscular
Due to the body’s inability to effectively synthesis protein without IGF-1, muscle destruction could occur faster than it is being replaced. Muscle atrophy, fibromyalgia, premature fatigue
and pain.
Low IGF-1 Levels
Bjersing et al. (2013)
Due to its difficulty to track, IGF-1 is becoming an
increasingly popular substance to abuse. However, excess of the hormone can be equally dangerous as a lack.
Abusive supplementation of IGF-1 is associated with: Hypoglycemia, seizures, jaw pain, myalgia and fluid retention.
IGF-1 in addition to its binding protein Lipohypertrophy (higher BMI), headaches, increased liver and
kidney size and altered liver function. Those who abuse IGF-1 and it’s binding protein also may have
acromegaly, or at least display many of its symptoms. Damaged cardiac muscle structure and performance, cardiac
valve dysfunction and reduced VO2 max.
Excess IGF-1 and Doping
Dystrophin deficiency impacted by blunted IGF-1
response Post-natal impacts Myotubules and myofiber growth in adult tissues
Further Studies
Grounds et. al. (2012) http://www.nature.com/nm/journal/v10/n6/fig_tab/nm0604-584_F1.html
Paoli study on resistance training with protein
levels Focus: myostatin, IGF-1 and cytokine release Myostatin and IGF-1 inverse relationship and
downregulation P38 MAPK stress kinase Observing TNF-α High protein diet
Further Studies
Paoli et. al. (2015) http://www.biocarta.com/pathfiles/
m_p38mapkpathway.asp
Questions?
Bjersing, J. L., Erlandsson, M., Bokarewa, M. I., & Mannerkorpi, K. (2013). Exercise and obesity in fibromyalgia: beneficial roles of IGF-1 and resistin? Arthritis Research & Therapy. 15(1), R34.
Doi, T., Shimada, H., Makizako, H., Tsumimoto, K., Hotta, R., Nakakubo, S., & Suzuki, T. (2015). Association of insulin-like growth factor-1 with mild cognitive impairment and slow gait speed. Neurobiology Of Aging, 36(2), 942-947. doi:10.1016/j.neurobiolaging.2014.10.035
Grounds, M. D., & Shavlakadze, T. (2012). Growing muscle has different sarcolemmal properties from adult muscle: A proposal with scientific and clinical implications. Neuromuscular Disorders, 22(1), 890-892. doi: 10.1002/bies.201000136
Paoli, A., Pacelli, Q. F., Neri, M., Toniolo, L., Cancellara, P., Canato, M., Moro, T., Quadrelli, M., Morra, A., Faggian, D., Plebani, M., Bianco, A., & Reggiani, C. (2015). Protein supplementation increases postexercise plasma myostatin concentration after 8 weeks of resistance training in young physically active subjects. Journal of Medicinal Food, 18(1), 137-143. doi: 10.1089/jmf.2014.0004
Guha, N., Cowan, D. A., Sönksen, P. H., & Holt, R. I. (2013). Insulin-like growth factor-I (IGF-I) misuse in athletes and potential methods for detection. Analytical and bioanalytical chemistry, 405(30), 9669-9683.
Jia, L., Li, Y. F., Wu, G. F., Song, Z. Y., Lu, H. Z., Song, C. C., Zhang, Q. L., Zhu, J. Y., Yang, G. S., & Shi, X. E. (2014). MiRNA-199a-3p Regulates C2C12 Myoblast Differentiation through IGF-1/AKT/mTOR Signal Pathway. International Journal of Molecular Sciences, 15(1), 296-308. doi: 10.3390/ijms15010296
Keisuke, H., & Kunihiro, T. (2014). Role of microRNAs in skeletal muscle hypertrophy. Frontiers In Physiology, 4(5), 1-7. doi:10.3389/fphys.2013.00408
Selected References