Ulrika Berg

Effect of acute endurance and strength exercise on circulating calcium‐regulating hormones and bone markers in young healthy males

Physical activity plays a role in the maintenance of the skeleton but the mechanical, metabolic and hormonal mechanisms involved are largely unknown. The influnence of acute endurance and strength exercise on circulating levels of calcitonin, parathyroid hormone (PTH), PTH‐related peptide (PTHrP), osteocalcin, carboxyterminal cross‐linked telopeptide of type I collagen (ICTP) and ionized calcium (Ca2+) was therefore evaluated. Eight healthy young males performed three exercise bouts on separate accasions: endurance exercise i.e. cycling on a cycle ergometer for 45 mim at 55% of Vo2max (E55%) and 15 min at 85% of Vo2max (E 85%) and strength exercise at 85% of three repetitions maximum using a legpress device (STR). Control experiments included the same subjects with the same time schedule but without exercise. Blood samples were taken before, immediately after exercise and during the recovery period. Hormones and bone markers were measured by use of various immunoassays. There was no obvious influence on calcitonin and PTHrP levels, whereas PTH was increased after strength exercise. ICTP and osteocalcin levels correlated positively at all times and showed regular variations. In comparison with the controls, ICTP levels showed a more pronounced decrease following physical activity whereas osteocalcin followed the same pattern as the controls except for after prolonged endurance exercise when a decrease was abolished. In conclusion, an increase in PTH after strength exercise and a pronounced decrease in ICTP after all exercise together with a relative increase in osteocalcin after prolonged endurance exercise might reflect some mechanisms involved in the positive effect of physical activity on bone mass.

Interstitial IGF-I in exercising skeletal muscle in women

OBJECTIVE To study interstitial IGF-I concentrations in resting and exercising skeletal muscle in relation to the circulating components of the IGF-IGF binding protein (IGFBP) system. DESIGN AND METHODS Seven women performed endurance exercise with 1 leg (Ex-leg) for 1 h. The resting leg (Rest-leg) served as a control. IGF-I was determined in microdialysate (MD) and was compared with veno-arterial (v-a) concentrations of circulating IGF-IGFBP components. RESULTS Median (range) basal MD-IGF-I was 0.87 (0.4-1.5) microg/l or 0.4 (0.2)% of total-IGF-I (t-IGF-I) determined in arterial serum and in the same concentration range as free dissociable IGF-I (f-IGF-I). Rest-leg MD-IGF-I decreased, reaching significance after exercise. Ex-leg MD-IGF-I was unchanged during exercise and declined after exercise at the level of significance (P = 0.05). There was a release of f-IGF-I from the Ex-leg into the circulation at the end of and shortly after exercise. A small but significant increase in circulating IGFBP-1 was detected at the end of exercise and IGFBP-1 increased further after exercise. Although interleukin-6 (IL-6) has been associated with IGFBP-3 proteolysis, the circulating molecular forms of IGFBP-3 remained unchanged in spite of an IL-6 release from the muscle compartment. CONCLUSIONS Circulating IGFBP-1 is related to interstitial IGF-I in resting muscle although the temporal relationship may not be simple. Further studies should explore the role of local release of IGF-I and its impact on IGF-I activity during contraction.

Free Insulin-Like Growth Factor I: Are We Hunting a Ghost?

During the last decade, there has been an increasing number of publications reporting concentrations of free dissociable insulin-like growth factor I (IGF-I) in serum or plasma. The goal for attempting to measure free IGF-I in a serum sample in vitro has been to obtain information about the bioactivity of IGF-I in target tissues, and thus relate a measurable parameter to biological responses such as longitudinal growth or glucose disappearance rate. In this review, the serum free IGF-I approach is placed into a physiological perspective. In addition, methodological aspects are discussed and suggestions for the validation of free IGF-I assays are presented.

Lack of sex differences in the IGF-IGFBP response to ultra endurance exercise.

The insulin‐like growth factor (IGF)–IGF binding proteins (BP) and the pituitary–gonadal axes were investigated during ultra endurance exercise in 16 endurance‐trained athletes (seven women). Median duration of the race was 6.3 days. Although food and drink were ad libitum, energy balance was negative. Blood samples were drawn before (PRE), at the end of (END) and 24 h after (POST24h) the race. Serum concentrations of total IGF‐I (t‐IGF‐I) and free IGF‐I (f‐IGF‐I) decreased by 33 (SD 38)% and 54 (19)%, respectively. The decrease in t‐IGF‐I appeared to be associated to the total energy deficit during the race. At END, the IGFBP‐3 fragmentation and IGFBP‐1 were increased but these changes did not predict changes in f‐IGF‐I. An increase in POST24h IGFBP‐2 levels in women was the only sex difference. Testosterone was decreased by 67 (12)% in the men and estradiol became undetectable in the women without any detectable increase in LH and/or FSH. In conclusion ultra endurance exercise results in similar IGF–IGFBP responses in men and women reflecting a catabolic state. IGFBP‐2 was the only exception, with increased levels in women after exercise. A concomitant decrease in gonadal hormones was not related to endocrine changes in the IGF–IGFBP axis but may be related to local changes in IGF‐I expression.

Acute interleukin-6 infusion increases IGFBP-1 but has no short-term effect on IGFBP-3 proteolysis in healthy men.

Human conditions of elevated interleukin-6 (IL-6) and transgenic mice overexpressing IL-6 have increased proteolytic degradation of insulin-like growth factor binding protein (IGFBP)-3. In addition, IL-6 alters the hepatic expression of insulin-like growth factor-I (IGF-I) and the IGFBPs in vitro. The aim of the present study was to investigate whether moderately elevated IL-6 levels have short-term effects on circulating IGF-I, IGFBP-1 and IGFBP-3 proteolysis in vivo. Healthy men received a 3-h IL-6 (n = 6) or saline (n = 6) infusion and blood samples were collected prior to and up to 8 h after the start of infusion. Free IGF-I, total IGF-I, IGFBP-1, insulin and cortisol were measured using immunoassays. Serum IGFBP-3 proteolysis was analyzed by Western immunoblot and by in vitro degradation of 125I-IGFBP-3. We found that IL-6 concentrations reaching approximately 100 pg/ml significantly increased IGFBP-1 after the end of infusion in the absence of changes in insulin. In addition, plasma levels of cortisol were increased in response to IL-6 during and after infusion compared to saline. There was no effect of IL-6 on IGFBP-3 proteolysis, total IGF-I or free dissociable IGF-I. These data suggest that moderately elevated levels of IL-6 such as in the post-operative state or after exercise may contribute to increased levels of IGFBP-1. Although this study does not exclude that high levels and/or prolonged exposure to IL-6 may induce IGFBP-3 proteolysis in sepsis or chronic inflammatory disease, it suggests that IL-6 released from exercising skeletal muscle is not directly involved in proteolysis of circulating IGFBP-3.

Calpain proteolysis of insulin-like growth factor binding protein (IGFBP) -2 and -3, but not of IGFBP-1.

Abstract Calpains are cytoplasmic Ca2+-regulated cysteine proteases that may regulate insulin-like growth factor (IGF)-independent actions of insulin-like growth factor binding proteins (IGFBPs) through IGFBP proteolysis. In this study, [125I]-labeled IGFBP-2 and -3, but not IGFBP-1, were proteolyzed by Ca2+-activated m-calpain in vitro. Degradation of higher concentrations of the recombinant proteins IGFBP-2 and -3 by m-calpain was dose-dependent, but was terminated within 20 min by autolysis. By subjecting proteolytic fragments to N-terminal amino acid sequence analysis, the primary cleavage sites in IGFBP-2 and -3 were localized to the non-conserved central linker regions. Using the biosensor technique, in vitro binding of m-calpain to IGFBP-3 was demonstrated to be a Ca2+-dependent reaction with a rapid on/off rate.