Reduced Fragmentation of IGFBP-2 and IGFBP-3 as a Potential Mechanism for Decreased Ratio of IGF-II to IGFBPs in Cerebrospinal Fluid in Response to Repeated Intrathecal Administration of Triamcinolone Acetonide in Patients With Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune disease of the brain and spinal cord causing a wide range of symptoms such as impaired walking capability, spasticity, fatigue, and pain. The insulin-like growth factor (IGF) system has regulatory functions for the induction of inflammatory pathways in experimental encephalomyelitis. We have therefore assessed expression and regulation of the IGF system on the level of IGFs and IGFBPs in serum and cerebrospinal fluid (CSF) in the course of four repeated triamcinolone acetonide (TCA) administrations in two female and four male MS patients. Sample series of 20 treatment cycles were analyzed. IGF-I and IGF-II were quantified by ELISAs, and IGFBPs were analyzed by quantitative Western ligand (qWLB) and Western immunoblotting (WIB) in order to differentiate intact and fragmented IGFBPs. The ratios of fragmented to intact IGFBP-2 and -3 were calculated in serum and CSF. Finally, the ratios of IGF-I and IGF-II to the total IGF-binding activity, quantified by qWLB, were determined as an indicator of IGF-related bioactivity. After the fourth TCA administration, the average level of IGF-I was increased in serum (p < 0.001). The increase of IGF-I concentrations in serum resulted in an increased ratio of IGF-I to IGFBPs in the circulation. By contrast in CSF, fragmentation of IGFBP-2 and IGFBP-3 and the ratio of IGF-II to intact IGFBPs were decreased at the fourth TCA administration (p < 0.01). Furthermore, reduced fragmentation of IGFBP-3 in CSF was accompanied by increased concentrations of intact IGFBP-3 (p < 0.001). We conclude that reduced fragmentation of IGFBPs and concomitant reduction of IGF-II to IGFBP ratios indicate regulation of bioactivity of IGF-II in CSF during repeated intrathecal TCA administration in MS patients.

Preparatory training attenuates drastic response of the insulin-like growth factor binding protein 1 at the point of maximal oxygen consumption in handball players.

BACKGROUND: Intensive exercise changes physiological need for glucose and several biochemical pathways responsible for its metabolism response. Among them are those which involve insulin, insulin-like growth factor (IGF-1), and IGF-binding proteins (IGFBPs). Different types and degrees of exercise, as well as an athlete's fitness, may induce a range of responses regarding concentrations and time needed for the alteration. The idea of the work was to find out whether and how insulin/IGF axis responds to additional physical activity in the already trained subjects and if so, is the adaptation potentially beneficial from the aspect of metabolic control. METHODS: The effect of 4-week intensive training on campus (preparatory training) on the levels of insulin, IGF-1, and IGFBPs during maximal progressive exercise test (MPET) on a treadmill was compared to the results obtained during MPET conducted after a regular training season of a female elite handball team (n = 17, age: 17 ± 1 years, height: 171 ± 8 cm, weight: 65 ± 8 kg, body mass index: 22 ± 1 kg/m2 at the beginning of the study; there were no significant changes at the end). Serum samples were obtained from players immediately before the test (basal), at the end of the test after reaching the point of maximal oxygen consumption (VO2max), and after recovery. RESULTS: The concentration of insulin decreased at VO2max, but remained higher in players after preparatory training (12.2 ± 2.5 mU/L vs. 8.9 ± 4.4 mU/L, p = 0.049). The level of IGFBP-1 decreased in players at VO2max in either case of training, but it remained much higher in tests performed after the preparatory regime than before (p = 0.029). Concentrations of IGF-1, IGFBP-2, -3, and -4 did not change significantly. CONCLUSION: The inverse relation between insulin and IGFBP-1 was lost during MPET, as these 2 molecules changed in the same direction. The results obtained suggest less severe stress-induced depression of insulin and IGFBP-1 after preparatory training. But another metabolic mechanism cannot be excluded, and that is potentially impaired insulin sensitivity resulting in higher level of IGFBP-1.

Skeletal effects of growth hormone and insulin-like growth factor-I therapy.

The growth hormone/insulin-like growth factor (GH/IGF) axis is critically important for the regulation of bone formation, and deficiencies in this system have been shown to contribute to the development of osteoporosis and other diseases of low bone mass. The GH/IGF axis is regulated by a complex set of hormonal and local factors which can act to regulate this system at the level of the ligands, receptors, IGF binding proteins (IGFBPs), or IGFBP proteases. A combination of in vitro studies, transgenic animal models, and clinical human investigations has provided ample evidence of the importance of the endocrine and local actions of both GH and IGF-I, the two major components of the GH/IGF axis, in skeletal growth and maintenance. GH- and IGF-based therapies provide a useful avenue of approach for the prevention and treatment of diseases such as osteoporosis.