Microdialysis-Assessed Exercised Muscle Reveals Localized and Differential IGFBP Responses to Unilateral Stretch Shortening Cycle Exercise

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2020 Jun 18

PMID 32547489

Citations 1

Authors

Bradley C Nindl

Juha Ahtiainen

Sheila S Gagnon

Ritva S Taipale

Joseph R Pierce

Brian J Martin

Meaghan E Beckner

M Lehti

Keijo Hakkinen

Heikki Kyrolainen

Affiliations

Soon will be listed here.

Abstract

Microdialysis allows for a preview into local muscle metabolism and can provide physiological insight that blood measurements cannot. To examine the potential differential IGF-I system regulation in interstitial fluid during unilateral stretch shortening cycle exercise. 10 men (26 ± 7 year) performed unilateral jumping [stretch shortening cycle (SSC) exercise at 50% of optimal jump height] until volitional fatigue on a sled apparatus. Biological sampling took place using a catheter inserted into an antecubital vein (serum), and 100 kDa microdialysis probes inserted into the thigh muscle of each exercise/control leg (dialysate). Serum was drawn before (Pre; -3 h) and after SSC [Post I (+0 h), II (+3 h), or III (+20 h)]; dialysate was sampled for 2 h before (Pre), during/immediately after (Ex), and 3 h into recovery (Rec) following SSC. IGF-I system parameters (free/total IGF-I and IGFBPs 1-6) were measured with immunoassays. Interstitial free IGF-I was estimated from dialysate IGF-I and relative recovery (ethanol) correction. Data were analyzed with repeated measures ANOVA. Serum total IGF-I remained elevated +3 h (Post II: 182.8 ± 37.6 vs. Pre: 168.3 ± 35.0 ng/mL, < 0.01), but returned to baseline by +20 h (Post III vs. Pre, = 0.31). No changes in serum free IGF-I were noted. Serum BP-1 and -3 increased over baseline, but not until + 20 h after SSC (Post III vs. Pre: 7.6 ± 4.9 vs. 3.7 ± 2.3 and 1,048.6 ± 269.2 vs. 891.4 ± 171.2 ng/mL, respectively). We observed a decreased serum BP-6 +3 h after SSC ( < 0.01), followed by a return to baseline at +20 h ( = 0.64 vs. Pre). There were no exercise-induced changes in serum BP-2, -4, or -5. Unlike serum, there were no changes in dialysate or interstitial free IGF-I in either leg ( > 0.05). Dialysate BP-1 remained increased in both exercise and control legs through 3 h into recovery (Rec vs. Pre, < 0.01). Dialysate BP-3 also demonstrated a prolonged elevation over Pre SSC concentrations, but in the exercise leg only (Ex and Rec vs. Pre, < 0.04). We observed a prolonged decrease in dialysate BP-5 (Ex and Rec vs. Pre, < 0.03) and an increase in BP-4 IP in the exercise leg only. There were no changes relative to Pre SSC in dialysate BP-2 or -6. : Unilateral exercise drives differential regulation of the IGF-I system at both local and systemic levels. More specifically, this is the first study to demonstrate that localized exercise increases IGFBP-3, IGFBP-4 and decreases in IGFBP-5 in muscle interstitial fluid.

Citing Articles

Insulin-like growth factor-I biocompartmentalization across blood, interstitial fluid and muscle, before and after 3 months of chronic resistance exercise.

Sterczala A, Pierce J, Barnes B, Urso M, Matheny R, Scofield D J Appl Physiol (1985). 2022; 133(1):170-182.

PMID: 35678743 PMC: 9291428. DOI: 10.1152/japplphysiol.00592.2021.

References

Nindl B, Castellani J, Young A, Patton J, Khosravi M, Diamandi A . Differential responses of IGF-I molecular complexes to military operational field training. J Appl Physiol (1985). 2003; 95(3):1083-9. DOI: 10.1152/japplphysiol.01148.2002. View

Nindl B, Kraemer W, Marx J, Arciero P, Dohi K, Kellogg M . Overnight responses of the circulating IGF-I system after acute, heavy-resistance exercise. J Appl Physiol (1985). 2001; 90(4):1319-26. DOI: 10.1152/jappl.2001.90.4.1319. View

Nindl B, Alemany J, Tuckow A, Kellogg M, Sharp M, Patton J . Effects of exercise mode and duration on 24-h IGF-I system recovery responses. Med Sci Sports Exerc. 2009; 41(6):1261-70. DOI: 10.1249/MSS.0b013e318197125c. View

Mukherjee A, Wilson E, Rotwein P . Insulin-like growth factor (IGF) binding protein-5 blocks skeletal muscle differentiation by inhibiting IGF actions. Mol Endocrinol. 2007; 22(1):206-15. PMC: 2194633. DOI: 10.1210/me.2007-0336. View

Awede B, Thissen J, Gailly P, Lebacq J . Regulation of IGF-I, IGFBP-4 and IGFBP-5 gene expression by loading in mouse skeletal muscle. FEBS Lett. 1999; 461(3):263-7. DOI: 10.1016/s0014-5793(99)01469-6. View

Nindl B, Pierce J . Insulin-like growth factor I as a biomarker of health, fitness, and training status. Med Sci Sports Exerc. 2009; 42(1):39-49. DOI: 10.1249/MSS.0b013e3181b07c4d. View

Bach L . What Happened to the IGF Binding Proteins?. Endocrinology. 2017; 159(2):570-578. DOI: 10.1210/en.2017-00908. View

Hoeflich A, Pintar J, Forbes B . Editorial: Current Perspectives on Insulin-Like Growth Factor Binding Protein (IGFBP) Research. Front Endocrinol (Lausanne). 2018; 9:667. PMC: 6255849. DOI: 10.3389/fendo.2018.00667. View

Kyrolainen H, Komi P . The function of neuromuscular system in maximal stretch-shortening cycle exercises: Comparison between power- and endurance-trained athletes. J Electromyogr Kinesiol. 2010; 5(1):15-25. DOI: 10.1016/s1050-6411(99)80002-9. View

10.

Berg U, Bang P . Exercise and circulating insulin-like growth factor I. Horm Res. 2005; 62 Suppl 1:50-8. DOI: 10.1159/000080759. View

11.

Nindl B, Tuckow A, Alemany J, Harman E, Rarick K, Staab J . Minimally invasive sampling of transdermal body fluid for the purpose of measuring insulin-like growth factor-I during exercise training. Diabetes Technol Ther. 2006; 8(2):244-52. DOI: 10.1089/dia.2006.8.244. View

12.

Moralez A, Maile L, Clarke J, Busby Jr W, Clemmons D . Insulin-like growth factor binding protein-5 (IGFBP-5) interacts with thrombospondin-1 to induce negative regulatory effects on IGF-I actions. J Cell Physiol. 2005; 203(2):328-34. DOI: 10.1002/jcp.20343. View

13.

Clemmons D . Role of IGF-binding proteins in regulating IGF responses to changes in metabolism. J Mol Endocrinol. 2018; 61(1):T139-T169. DOI: 10.1530/JME-18-0016. View

14.

Ewton D, Coolican S, Mohan S, Chernausek S, FLORINI J . Modulation of insulin-like growth factor actions in L6A1 myoblasts by insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5: a dual role for IGFBP-5. J Cell Physiol. 1998; 177(1):47-57. DOI: 10.1002/(SICI)1097-4652(199810)177:1<47::AID-JCP5>3.0.CO;2-E. View

15.

Hickner R, Rosdahl H, Borg I, Ungerstedt U, Jorfeldt L, Henriksson J . The ethanol technique of monitoring local blood flow changes in rat skeletal muscle: implications for microdialysis. Acta Physiol Scand. 1992; 146(1):87-97. DOI: 10.1111/j.1748-1716.1992.tb09396.x. View

16.

Bach L . IGF-binding proteins. J Mol Endocrinol. 2017; 61(1):T11-T28. DOI: 10.1530/JME-17-0254. View

17.

Nindl B, Santtila M, Vaara J, Hakkinen K, Kyrolainen H . Circulating IGF-I is associated with fitness and health outcomes in a population of 846 young healthy men. Growth Horm IGF Res. 2011; 21(3):124-8. DOI: 10.1016/j.ghir.2011.03.001. View

18.

Miller B, Olesen J, Hansen M, Dossing S, Crameri R, Welling R . Coordinated collagen and muscle protein synthesis in human patella tendon and quadriceps muscle after exercise. J Physiol. 2005; 567(Pt 3):1021-33. PMC: 1474228. DOI: 10.1113/jphysiol.2005.093690. View

19.

Nicol C, Avela J, Komi P . The stretch-shortening cycle : a model to study naturally occurring neuromuscular fatigue. Sports Med. 2006; 36(11):977-99. DOI: 10.2165/00007256-200636110-00004. View

20.

Berg U, Gustafsson T, Sundberg C, Carlsson-Skwirut C, Hall K, Jakeman P . Local changes in the insulin-like growth factor system in human skeletal muscle assessed by microdialysis and arterio-venous differences technique. Growth Horm IGF Res. 2006; 16(4):217-23. DOI: 10.1016/j.ghir.2006.05.004. View