The IGF-IGFBP system in aerobic exercise : with focus on skeletal muscle
Year: 2007
Type: dissertation
Abstract: Activity induced skeletal muscle adaptation has been suggested to be\nmediated largely by intrinsic factors, such as insulin-like growth factor\n(IGF)-I. IGF-I stimulates muscle glucose and amino acid uptake and\npromotes anabolism. IGF-I is bound to a family of high affinity IGF\nbinding proteins (IGFBP 1-6) which regulate access of systemic IGF-I to\ntissues and determines local IGF-I bioavailability. These functions are\nmodulated by posttranslational modifications of IGFBPs such as\nproteolysis and phosphorylation. Levels of unbound bioavailable IGF-I\nhave not previously been explored in muscle or other tissues.\n\nThis thesis focuses on IGF-I protein levels in the human skeletal muscle\ninterstitial fluid. In models of endurance exercise in both sexes and in\nvitro, we explored factors expected to regulate local muscle IGF-I\nactivity including circulating IGF-I and IGFBPs under the influence of\ninterleukin-6 (IL-6) and sex hormones. This was possible by the\ndevelopment of a microdialysis approach. Unbound IGF-I in human skeletal\nmuscle interstitial fluid was detected in microdialysate (md-IGF-I)\ncollected from an intramuscular probe. Basal md-IGF-I at rest was in the\nsame concentration range as free (unbound) IGF-I in serum and correlated\nwith total (bound plus unbound) IGF-I. Endurance exercise with one leg\n(45 or 60 min), decreased md-IGF-I in the resting leg concomitantly with\nincreased circulating IGFBP-1. This is the first evidence to support that\nincreasing circulating IGFBP-1 decreases local muscle IGF-I\nbioavailability. Exercising leg md-IGF-I did not decrease and free IGF-I\nwas released to the regional circulation (v-a difference) but with lack\nof correlation to systemic changes. We conclude that the regulation of\nunbound IGF-I in the exercising muscle is less affected by systemic\nfactors than the resting muscle. Proteases partially cleave IGFBPs into\ndistinct fragments and increase IGF bioavailability. This process may\ncontribute to increased local IGF-I in exercising muscle. IGFBP-3 was\ncleaved during extended ultra endurance exercise (UEE). Since this may\nreflect local IGFBP-3 proteolysis we examined a Ca2+ - activated muscle\nprotease m-calpain. In vitro, m-Calpain cleaved IGFBP-2 and -3 into\nfragments that we identified by N-terminal amino acid sequencing. Gonadal\nfunction was suppressed by UEE but with no major sex differences and no\ncorrelation to changes in IGF-IGFBP. For the first time, we demonstrated\na net release of IL-6 from exercising muscle in women. The role of IL-6\nwas specifically addressed by a 3 h IL-6 infusion that increased IGFBP-1\nconcentrations with no effect on circulating free IGF-I or IGFBP-3.\n\nThe results from these studies shed new light on the regulation of\nskeletal muscle tissue IGF-I bioavailability which may be of importance\nfor exercise adaptation and resting metabolism and anabolism.
Source: Figshare
Author: Ulrika Berg
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1002110307