BioIGF-LR (4mg)

IGF-1 Research

IGF-1 signaling is one of the more closely mapped pathways in skeletal muscle research. Reduced IGF-1 signaling has been associated with myofibre atrophy in aging models, alongside changes in activity, nutrition, and motor neuron loss [1]. Reviews of the IGF-1/Akt/mTOR cascade describe it as the primary link between mechanical loading and muscle protein synthesis, and identify age-related dysregulation of that cascade as a research target [2].

Fat metabolism and skeletal muscle anabolic pathways run through overlapping signaling routes. Both involve PI3K/Akt and MAPK/ERK activation downstream of receptor tyrosine kinase activity, which is why IGF-1R occupancy is a shared readout across adipose and myogenic models [3].

At the cellular level, IGF-1 is associated with muscle satellite cell proliferation and myogenic differentiation, with IGF-1R activation of PI3K/Akt reported as the operative step in myoblast proliferation models [3]. IGF-1 signaling has also been mapped onto bone research, where it interacts with parathyroid hormone signaling and integrin mechanotransduction pathways in osteogenesis models [4].

Metabolic Research Findings

Reviews of IGF-1 deficiency describe associations with altered lipid profiles, insulin resistance, and glucose handling across animal and observational work [5]. Separate review work has characterized the short-term metabolic action of IGF-1 as insulin-like and the long-term action as growth-factor-like, with outcomes that vary by tissue and by concentration [6].

The concentration dependence runs in both directions. IGF1 expression was increased in adipose tissue in obesity models, and genetic down-regulation of IGF1 normalized lipogenic gene expression and energy metabolism in a diet-induced rodent model [7].

Cognitive and Neuronal Research Findings

IGF-1 receptor activity has been documented on both neurons and neuroglia, with reported involvement in myelination, synaptogenesis, and astrocytic homeostatic function [8]. Reviews of IGF signaling in neurodegeneration models describe disrupted PI3K/Akt and MAPK signaling downstream of IGF-1R as a recurring feature, alongside altered brain energy metabolism [9].

Akt phosphorylation inactivates Glycogen Synthase Kinase-3 Beta (GSK-3β). In rodent models, IGF-1 application restored activity in the PI3K/Akt/GSK-3β axis and reversed changes in apoptotic and inflammatory markers [11].

Concentration matters here as well. An eight-year follow-up study in adult study populations reported that the highest IGF-1 quintile was associated with lower processing capacity and global cognition scores at follow-up, with the authors proposing that intermediate concentrations track with better cognitive scores rather than high ones [10].

Sleep and Circadian Signaling Research

Circulating IGF-1 follows a circadian pattern, and its entry into the brain is activity-dependent. Work in mice with disrupted IGF-1 receptor activity in orexin neurons reported lower hypothalamic orexin levels, altered electrocorticographic patterns with predominant slow wave activity, and reduced sleep onset latency [13].

Follow-on work from the same group reported that IGF-1 modulates orexin levels and hepatic expression of circadian entrainment genes in an orexin-dependent manner, positioning IGF-1R signaling at the junction between metabolic state and circadian activity [14].

Observational work has reported lower serum IGF-1 concentrations in adult study populations with chronic insomnia disorder, with concentrations correlating with polysomnography-measured slow wave sleep time [12]. Rodent sleep deprivation models reported down-regulated IGF-1 alongside reduced PI3K/Akt/GSK-3β activation in brain tissue [11].

Taken together, these findings point toward IGF-1 signaling being concentration-dependent and tissue-dependent, which is a reason laboratories value compounds with a defined and extended serum stability period.

References

1. Grounds MD (2002). Reasons for the degeneration of ageing skeletal muscle: a central role for IGF-1 signalling. Biogerontology 3(1-2):19-24. https://doi.org/10.1023/a:1015234709314
2. Barclay RD, Burd NA, Tyler C, Tillin NA, Mackenzie RW (2019). The Role of the IGF-1 Signaling Cascade in Muscle Protein Synthesis and Anabolic Resistance in Aging Skeletal Muscle. Frontiers in Nutrition 6:146. https://doi.org/10.3389/fnut.2019.00146
3. Ahmad SS, Ahmad K, Lee EJ, Lee Y-H, Choi I (2020). Implications of Insulin-Like Growth Factor-1 in Skeletal Muscle and Various Diseases. Cells 9(8):1773. https://doi.org/10.3390/cells9081773
4. Tahimic CGT, Wang Y, Bikle DD (2013). Anabolic effects of IGF-1 signaling on the skeleton. Frontiers in Endocrinology 4:6. https://doi.org/10.3389/fendo.2013.00006
5. Aguirre GA, De Ita JR, de la Garza RG, Castilla-Cortazar I (2016). Insulin-like growth factor-1 deficiency and metabolic syndrome. Journal of Translational Medicine 14:3. https://doi.org/10.1186/s12967-015-0762-z
6. AsghariHanjani N, Vafa M (2019). The role of IGF-1 in obesity, cardiovascular disease, and cancer. Medical Journal of the Islamic Republic of Iran 33:56. https://doi.org/10.34171/mjiri.33.56
7. Rong P, Mu Y, Wang M, Chen L, Liu F, Jin Y, Feng W, Zhou K, Liang H, Wang H-Y, Chen S (2025). Targeting IGF1 to alleviate obesity through regulating energy expenditure and fat deposition. Science China Life Sciences 68(6):1662-1675. https://doi.org/10.1007/s11427-024-2768-y
8. Hayes CA, Wilson D, De Leon MA, Mustapha MJ, Morales S, Odden MC, Ashpole NM (2025). Insulin-like growth factor-1 and cognitive health: Exploring cellular, preclinical, and clinical dimensions. Frontiers in Neuroendocrinology 76:101161. https://doi.org/10.1016/j.yfrne.2024.101161
9. Miao J, Zhang Y, Su C, Zheng Q, Guo J (2025). Insulin-Like Growth Factor Signaling in Alzheimer’s Disease: Pathophysiology and Therapeutic Strategies. Molecular Neurobiology 62(3):3195-3225. https://doi.org/10.1007/s12035-024-04457-1
10. Tumati S, Burger H, Martens S, van der Schouw YT, Aleman A (2016). Association between Cognition and Serum Insulin-Like Growth Factor-1 in Middle-Aged & Older Men: An 8 Year Follow-Up Study. PLoS One 11(4):e0154450. https://doi.org/10.1371/journal.pone.0154450
11. Wan Y, Gao W, Zhou K, Liu X, Jiang W, Xue R, Wu W (2022). Role of IGF-1 in neuroinflammation and cognition deficits induced by sleep deprivation. Neuroscience Letters 776:136575. https://doi.org/10.1016/j.neulet.2022.136575
12. Zhang Y, Sun Q, Li H, Wang D, Wang Y, Wang Z (2023). Lower serum insulin-like growth factor 1 concentrations in patients with chronic insomnia disorder. Frontiers in Psychiatry 14:1102642. https://doi.org/10.3389/fpsyt.2023.1102642
13. Zegarra-Valdivia JA, Pignatelli J, Fernandez de Sevilla ME, Fernandez AM, Munive V, Martinez-Rachadell L, Nuñez A, Torres Aleman I (2020). Insulin-like growth factor I modulates sleep through hypothalamic orexin neurons. FASEB Journal 34(12):15975-15990. https://doi.org/10.1096/fj.202001281RR
14. Pignatelli J, Fernandez de Sevilla ME, Sperber J, Horrillo D, Medina-Gomez G, Torres Aleman I (2022). Insulin-like Growth Factor I Couples Metabolism with Circadian Activity through Hypothalamic Orexin Neurons. International Journal of Molecular Sciences 23(9):4679. https://doi.org/10.3390/ijms23094679