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LR3 IGF-I ("IGF1-LR3")'s biological half life is remarkably & profoundly short rather than long.
Its clearance from the blood depends primarily on IGFBP-3 levels, that are increased, probably dose-dependently, by rhGH. Nobody knows its estimated t1/2 in healthy adults, but it should be administered at least twice daily, if not more frequently.
From my notes (granted, it takes a bit more understanding that “it’s ‘Long’ R3, bro, lol”):
LR3 IGF-I is more potent than IGF-I when the peptides are given by injection, and particularly with twice daily injection due to its rapid clearance from plasma. [1]. The affinity for binding is four- to five- fold larger for LR3 IGF-I than IGF-I, and it is rapidly cleared from the plasma as a consequence of its resistance to binding to the IGFBPs. [1].
IGFBPs profiles & functions
- human skeletal muscle cells: abundant IGFBP-3; high affinity -BP-2 & -BP-4; -3, & -5 [3]
- fetal cells: <<IGFBP-3, -2 & no -4
- rat L6: IGFBP-4, -5, and -6
- rat C2: only IGFBP-5. [2].
IGFBPs modulate IGF activity by extending the half-life of the IGFs and by either potentiating or inhibiting binding of the IGFs to their receptors. [3].
From [3]:
Although muscle satellite cells were identified almost 40 years ago, little is known about the induction of their proliferation and differentiation in response to physiological/pathological stimuli or to growth factors/cytokines. In order to investigate the role of the insulin-like growth factor (IGF)/IGF binding protein (IGFBP) system in adult human myoblast differentiation we have developed a primary human skeletal muscle cell model. We show that under low serum media (LSM) differentiating conditions, the cells secrete IGF binding proteins-2, -3, -4 and -5. Intact IGFBP-5 was detected at days 1 and 2 but by day 7 in LSM it was removed by proteolysis. IGFBP-4 levels were also decreased at day 7 in the presence of IGF-I, potentially by proteolysis. In contrast, we observed that IGFBP-3 initially decreased on transfer of cells into LSM but then increased with myotube formation. Treatment with 20 ng/ml tumour necrosis factor-alpha (TNFalpha), which inhibits myoblast differentiation, blocked IGFBP-3 production and secretion whereas 30 ng/ml IGF-I, which stimulates myoblast differentiation, increased IGFBP-3 secretion. The TNFalpha-induced decrease in IGFBP-3 production and inhibition of differentiation could not be rescued by addition of IGF-I. LongR(3)IGF-I, which does not bind to the IGFBPs, had a similar effect on differentiation and IGFBP-3 secretion as IGF-I, both with and without TNFalpha, confirming that increased IGFBP-3 is not purely due to increased stability conferred by binding to IGF-I. Furthermore reduction of IGFBP-3 secretion using antisense oligonucleotides led to an inhibition of differentiation. Taken together these data indicate that IGFBP-3 supports myoblast differentiation.
From the INCRELEX pamphlet:
Clearance of [IGF-I and its analogues] is inversely proportional to IGF binding protein-3 (IGFBP-3) levels.
Normal (healthy) clearance is 0.01 L/hr/kg (because normal concentrations of IGFBP-3, to which clearance is inversely proportional, is 3 micrograms/mL IGFBP-3).
From [4]:
rats; protocol: continuous subcutaneous infusion ~1.5mg * kg⁻¹ daily * 28 days (0.125μL*h⁻¹)
No significant effect of LR3 IGF-I on muscle contractile properties, mass, force capacity, nor specific force!
↓IGF-I (serum), ↓median myofiber CSA, indicating that IGFBP interaction is needed to maintain or augment muscle myofiber size, oxidative capacity!
_______________________
References:
[1] Tomas, F. M., Lemmey, A. B., Read, L. C., & Ballard, F. J. (1996). Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection. Journal of Endocr inology, 150(1), 77–84. doi:10.1677/joe.0.1500077
[2] Crown, A. (2000). Characterisation of the IGF system in a primary adult human skeletal muscle cell model, and comparison of the effects of insulin and IGF-I on protein metabolism. Journal of Endocrinology, 167(3), 403–415. doi:10.1677/joe.0.1670403
[3] Foulstone, E. J., Savage, P. B., Crown, A. L., Holly, J. M. P., & Stewart, C. E. H. (2003). Role of insulin-like growth factor binding protein-3 (IGFBP-3) in the differentiation of primary human adult skeletal myoblasts. Journal of Cellular Physiology, 195(1), 70–79. doi:10.1002/jcp.10227
[4] Gehrig SM, Ryall JG, Schertzer JD, Lynch GS. Insulin-like growth factor-I analogue protects muscles of dystrophic mdx mice from contraction-mediated damage. Exp Physiol. 2008 Nov;93(11):1190-8. doi: 10.1113/expphysiol.2008.042838. Epub 2008 Jun 20.
Its clearance from the blood depends primarily on IGFBP-3 levels, that are increased, probably dose-dependently, by rhGH. Nobody knows its estimated t1/2 in healthy adults, but it should be administered at least twice daily, if not more frequently.
From my notes (granted, it takes a bit more understanding that “it’s ‘Long’ R3, bro, lol”):
LR3 IGF-I is more potent than IGF-I when the peptides are given by injection, and particularly with twice daily injection due to its rapid clearance from plasma. [1]. The affinity for binding is four- to five- fold larger for LR3 IGF-I than IGF-I, and it is rapidly cleared from the plasma as a consequence of its resistance to binding to the IGFBPs. [1].
IGFBPs profiles & functions
- human skeletal muscle cells: abundant IGFBP-3; high affinity -BP-2 & -BP-4; -3, & -5 [3]
- fetal cells: <<IGFBP-3, -2 & no -4
- rat L6: IGFBP-4, -5, and -6
- rat C2: only IGFBP-5. [2].
IGFBPs modulate IGF activity by extending the half-life of the IGFs and by either potentiating or inhibiting binding of the IGFs to their receptors. [3].
From [3]:
Although muscle satellite cells were identified almost 40 years ago, little is known about the induction of their proliferation and differentiation in response to physiological/pathological stimuli or to growth factors/cytokines. In order to investigate the role of the insulin-like growth factor (IGF)/IGF binding protein (IGFBP) system in adult human myoblast differentiation we have developed a primary human skeletal muscle cell model. We show that under low serum media (LSM) differentiating conditions, the cells secrete IGF binding proteins-2, -3, -4 and -5. Intact IGFBP-5 was detected at days 1 and 2 but by day 7 in LSM it was removed by proteolysis. IGFBP-4 levels were also decreased at day 7 in the presence of IGF-I, potentially by proteolysis. In contrast, we observed that IGFBP-3 initially decreased on transfer of cells into LSM but then increased with myotube formation. Treatment with 20 ng/ml tumour necrosis factor-alpha (TNFalpha), which inhibits myoblast differentiation, blocked IGFBP-3 production and secretion whereas 30 ng/ml IGF-I, which stimulates myoblast differentiation, increased IGFBP-3 secretion. The TNFalpha-induced decrease in IGFBP-3 production and inhibition of differentiation could not be rescued by addition of IGF-I. LongR(3)IGF-I, which does not bind to the IGFBPs, had a similar effect on differentiation and IGFBP-3 secretion as IGF-I, both with and without TNFalpha, confirming that increased IGFBP-3 is not purely due to increased stability conferred by binding to IGF-I. Furthermore reduction of IGFBP-3 secretion using antisense oligonucleotides led to an inhibition of differentiation. Taken together these data indicate that IGFBP-3 supports myoblast differentiation.
From the INCRELEX pamphlet:
Clearance of [IGF-I and its analogues] is inversely proportional to IGF binding protein-3 (IGFBP-3) levels.
Normal (healthy) clearance is 0.01 L/hr/kg (because normal concentrations of IGFBP-3, to which clearance is inversely proportional, is 3 micrograms/mL IGFBP-3).
From [4]:
rats; protocol: continuous subcutaneous infusion ~1.5mg * kg⁻¹ daily * 28 days (0.125μL*h⁻¹)
No significant effect of LR3 IGF-I on muscle contractile properties, mass, force capacity, nor specific force!
↓IGF-I (serum), ↓median myofiber CSA, indicating that IGFBP interaction is needed to maintain or augment muscle myofiber size, oxidative capacity!
_______________________
References:
[1] Tomas, F. M., Lemmey, A. B., Read, L. C., & Ballard, F. J. (1996). Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection. Journal of Endocr inology, 150(1), 77–84. doi:10.1677/joe.0.1500077
[2] Crown, A. (2000). Characterisation of the IGF system in a primary adult human skeletal muscle cell model, and comparison of the effects of insulin and IGF-I on protein metabolism. Journal of Endocrinology, 167(3), 403–415. doi:10.1677/joe.0.1670403
[3] Foulstone, E. J., Savage, P. B., Crown, A. L., Holly, J. M. P., & Stewart, C. E. H. (2003). Role of insulin-like growth factor binding protein-3 (IGFBP-3) in the differentiation of primary human adult skeletal myoblasts. Journal of Cellular Physiology, 195(1), 70–79. doi:10.1002/jcp.10227
[4] Gehrig SM, Ryall JG, Schertzer JD, Lynch GS. Insulin-like growth factor-I analogue protects muscles of dystrophic mdx mice from contraction-mediated damage. Exp Physiol. 2008 Nov;93(11):1190-8. doi: 10.1113/expphysiol.2008.042838. Epub 2008 Jun 20.