The IGF-IGFBP system in aerobic exercise : with focus on skeletal muscle
Author: Berg, Ulrika
Date: 2007-11-16
Location: Skandiasalen, Astrid Lindgrens Barnsjukhus, Q2:01 (plan 1)
Time: 09.00
Department: Institutionen för kvinnors och barns hälsa / Department of Women's and Children's Health
View/ Open:
thesis.pdf (877.4Kb)
Abstract
Activity induced skeletal muscle adaptation has been suggested to be
mediated largely by intrinsic factors, such as insulin-like growth factor
(IGF)-I. IGF-I stimulates muscle glucose and amino acid uptake and
promotes anabolism. IGF-I is bound to a family of high affinity IGF
binding proteins (IGFBP 1-6) which regulate access of systemic IGF-I to
tissues and determines local IGF-I bioavailability. These functions are
modulated by posttranslational modifications of IGFBPs such as
proteolysis and phosphorylation. Levels of unbound bioavailable IGF-I
have not previously been explored in muscle or other tissues.
This thesis focuses on IGF-I protein levels in the human skeletal muscle
interstitial fluid. In models of endurance exercise in both sexes and in
vitro, we explored factors expected to regulate local muscle IGF-I
activity including circulating IGF-I and IGFBPs under the influence of
interleukin-6 (IL-6) and sex hormones. This was possible by the
development of a microdialysis approach. Unbound IGF-I in human skeletal
muscle interstitial fluid was detected in microdialysate (md-IGF-I)
collected from an intramuscular probe. Basal md-IGF-I at rest was in the
same concentration range as free (unbound) IGF-I in serum and correlated
with total (bound plus unbound) IGF-I. Endurance exercise with one leg
(45 or 60 min), decreased md-IGF-I in the resting leg concomitantly with
increased circulating IGFBP-1. This is the first evidence to support that
increasing circulating IGFBP-1 decreases local muscle IGF-I
bioavailability. Exercising leg md-IGF-I did not decrease and free IGF-I
was released to the regional circulation (v-a difference) but with lack
of correlation to systemic changes. We conclude that the regulation of
unbound IGF-I in the exercising muscle is less affected by systemic
factors than the resting muscle. Proteases partially cleave IGFBPs into
distinct fragments and increase IGF bioavailability. This process may
contribute to increased local IGF-I in exercising muscle. IGFBP-3 was
cleaved during extended ultra endurance exercise (UEE). Since this may
reflect local IGFBP-3 proteolysis we examined a Ca2+ - activated muscle
protease m-calpain. In vitro, m-Calpain cleaved IGFBP-2 and -3 into
fragments that we identified by N-terminal amino acid sequencing. Gonadal
function was suppressed by UEE but with no major sex differences and no
correlation to changes in IGF-IGFBP. For the first time, we demonstrated
a net release of IL-6 from exercising muscle in women. The role of IL-6
was specifically addressed by a 3 h IL-6 infusion that increased IGFBP-1
concentrations with no effect on circulating free IGF-I or IGFBP-3.
The results from these studies shed new light on the regulation of
skeletal muscle tissue IGF-I bioavailability which may be of importance
for exercise adaptation and resting metabolism and anabolism.
List of papers:
I. U. Berg, J.K. Enqvist, C.M. Mattson, C. Carlsson-Skwirut, C.J. Sundberg, B. Ekblom, P. Bang (2006). "Lack of sex differences in the IGF-IGFBP response to ultra endurance exercise." (Submitted)
II. Berg U, Gustafsson T, Sundberg CJ, Carlsson-Skwirut C, Hall K, Jakeman P, Bang P (2006). "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 16(4): 217-23. Epub 2006 Aug 14
Pubmed
III. Berg U, Gustafsson T, Sundberg CJ, Kaijser L, Carlsson-Skwirut C, Bang P (2007). "Interstitial IGF-I in exercising skeletal muscle in women." Eur J Endocrinol 157(4): 427-435
Pubmed
IV. Pihl S, Carlsson-Skwirut C, Berg U, Ekström K, Bang P (2006). "Acute interleukin-6 infusion increases IGFBP-1 but has no short-term effect on IGFBP-3 proteolysis in healthy men." Horm Res 65(4): 177-84. Epub 2006 Mar 20
Pubmed
V. Berg U, Bang P, Carlsson-Skwirut C (2007). "Calpain proteolysis of insulin-like growth factor binding protein (IGFBP) -2 and -3, but not of IGFBP-1." Biol Chem 388(8): 859-63
Pubmed
I. U. Berg, J.K. Enqvist, C.M. Mattson, C. Carlsson-Skwirut, C.J. Sundberg, B. Ekblom, P. Bang (2006). "Lack of sex differences in the IGF-IGFBP response to ultra endurance exercise." (Submitted)
II. Berg U, Gustafsson T, Sundberg CJ, Carlsson-Skwirut C, Hall K, Jakeman P, Bang P (2006). "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 16(4): 217-23. Epub 2006 Aug 14
Pubmed
III. Berg U, Gustafsson T, Sundberg CJ, Kaijser L, Carlsson-Skwirut C, Bang P (2007). "Interstitial IGF-I in exercising skeletal muscle in women." Eur J Endocrinol 157(4): 427-435
Pubmed
IV. Pihl S, Carlsson-Skwirut C, Berg U, Ekström K, Bang P (2006). "Acute interleukin-6 infusion increases IGFBP-1 but has no short-term effect on IGFBP-3 proteolysis in healthy men." Horm Res 65(4): 177-84. Epub 2006 Mar 20
Pubmed
V. Berg U, Bang P, Carlsson-Skwirut C (2007). "Calpain proteolysis of insulin-like growth factor binding protein (IGFBP) -2 and -3, but not of IGFBP-1." Biol Chem 388(8): 859-63
Pubmed
Issue date: 2007-10-26
Rights:
Publication year: 2007
ISBN: 978-91-7357-379-5
Statistics
Total Visits
Views | |
---|---|
The ...(legacy) | 639 |
The ... | 137 |
Total Visits Per Month
October 2023 | November 2023 | December 2023 | January 2024 | February 2024 | March 2024 | April 2024 | |
---|---|---|---|---|---|---|---|
The ... | 1 | 5 | 1 | 3 | 0 | 0 | 0 |
File Visits
Views | |
---|---|
thesis.pdf(legacy) | 505 |
thesis.pdf | 241 |
thesis.pdf.txt(legacy) | 2 |
Top country views
Views | |
---|---|
United States | 317 |
China | 72 |
Sweden | 63 |
Germany | 59 |
South Korea | 17 |
Russia | 16 |
Finland | 10 |
United Kingdom | 10 |
Denmark | 8 |
Hungary | 6 |
Top cities views
Views | |
---|---|
Sunnyvale | 29 |
Romeo | 27 |
Beijing | 22 |
Kiez | 20 |
Shenzhen | 16 |
Seoul | 14 |
Lansing | 12 |
Nürnberg | 11 |
Stockholm | 10 |
Ballerup | 8 |