Free insulin-like growth factors – measurements and relationships to growth hormone secretion and glucose homeostasis

Frystyk, Jan

doi:10.1016/j.ghir.2004.06.001

Cited by 307 publications

(297 citation statements)

References 352 publications

(613 reference statements)

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“…Furthermore,s erum total IGF-I remained unchanged during the OGTT and the same wast ruef or free IGF-I, despite the decrease in IGFBP-1 and rather stable IGFBP-2. Previous studies from our laboratory, as well as from others, have uniformlyshown thatserum-free IGF-I determined by either ultrafiltration or ac ommercial IRMA remains unchanged after oral glucose, as well as aftermeal intake (48).Ont he other hand, levels of bioactiveIGF-I decreased significantlyin cirrhotic patients and the samet endency wasa lso observed in healthyc ontrols during the OGTT ( P Z 0.052). This finding argues against the observation by Bereket and co-workers( 49), which indicated thati n response to food (or glucose) intake, changes in IGFBP-1 concentrations within the physiological range would not sufficientlya ffect IGF-Ib ioactivity by limitingt he availability of free IGF-I.…”

Section: Discussionsupporting

confidence: 56%

Changes in bioactive IGF-I and IGF-binding protein-1 during an oral glucose tolerance test in patients with liver cirrhosis

et al. 2006

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Objective :L iver cirrhosis is characterized by reduced circulating IGF-I and this has been linked to an adverse clinical outcome.Therefore, we investigated the dynamic changes in circulating total, free, and bioactiveI GF-I, IGF-binding protein (IGFBP)-1, IGFBP-2, and IGFBP-1-bound IGF-I (binarycomplex) during an oral glucose tolerance test (OGTT) in patients with liver cirrhosis. Methods:Seven Caucasian males with liver cirrhosis and seven healthymales matched for age (54.4G 3.2 vs 54.6G 4.4 years) and body mass index( 25.3G 1.2 vs 25.9G 1.3 kg/m 2 )w ere studied. Blood samples were drawn at 0, 30, 60, 90, 120, 150, and 180 min for determination of serum total and free IGF-I, IGFBP-1, IGFBP-2, and binarycomplex, while bioactiveIGF-I wasmeasured at 0, 30, 60, 120, and 180 min. Results:Incomparison with healthysubjects, baseline levels of total (47%), free (36%), and bioactive IGF-I (51%) were lower,w hile IGFBP-1 (268%) wash igher ( P ! 0.05), IGFBP-2 (172%) tended to be higher ( P O 0.05), and the binarycomplexunchanged ( w 100%) in cirrhotic patients. Serum total and free IGF-I, and IGFBP-2 remained unchangedinb oth study groups during the OGTT.B ioactiveIGF-I decreased by 29% from baseline to 60 min in cirrhotic patients and remained low at the end of the OGTT ( P ! 0.05). As imilar tendency waso bservedi nh ealthyc ontrols ( P Z 0.052). Concomitantly, IGFBP-1, binarycomplex, and IGFBP-1 saturation indexd ecreased significantlyi nb oth groups. The disappearance of the binarycomplex wasa bout twofold faster than that of IGFBP-1 ( P ! 0.05). Conclusion:D espite unchangedc oncentrations of total and free IGF-I, bioactive IGF-I declined significantlya fter an oral glucose load in patients with liverc irrhosis and the same tendency was observedinhealthysubjects. We speculate that the reduction in bioactiveIGF-I mayberelated to the higher levels of free IGFBP-1 and the faster disappearance of IGFBP-1-bound IGF-I. 155 285-292 European Journal of Endocrinology

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Section: Discussionsupporting

confidence: 56%

Changes in bioactive IGF-I and IGF-binding protein-1 during an oral glucose tolerance test in patients with liver cirrhosis

et al. 2006

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“…Thus, at the serum level, IGFBP3 is GH-dependent (37), but at the transcriptional level is independent of GH (38). In some diseases, such as T1D and obesity, the serum IGF1 concentration is often within the normal range, whereas the GH level is high, reflecting some degree of disintegration of the GH/IGF1 axis (39). We suggest that this type of disintegration of the GH/IGF1 axis may exist to some extent also in subjects seroconverting to positivity for diabetes-associated autoantibodies.…”

Section: Discussionmentioning

confidence: 99%

Circulating IGF1 and IGFBP3 in relation to the development of β-cell autoimmunity in young children

Peet

Hämäläinen

Kool

et al. 2015

European Journal of Endocrinology

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Objective: This study aimed at investigating the role of IGF1 and IGF binding protein 3 (IGFBP3) in the development of b-cell autoimmunity. Methods: Five hundred and sixty-three subjects with HLA-conferred susceptibility to type 1 diabetes (T1D) were monitored for signs of seroconversion to positivity for insulin and/or GAD, IA2, and zinc transporter 8 autoantibodies by the age of 3 years. In 40 subjects who developed at least one autoantibody, IGF1 and IGFBP3 plasma concentrations were measured and compared with 80 control subjects who remained negative for autoantibodies, and were matched for age, sex, country of origin, and HLA genotype. The increments of IGF1, IGFBP3, and IGF1/IGFBP3 molar ratio before and after seroconverison were compared with corresponding time intervals in controls. Results: The IGF1 concentrations at the age of 12 months and the IGF1/IGFBP3 ratio at the age of 24 months were lower in the autoantibody-positive children (P!0.05). The increase in circulating IGFBP3 was significantly higher in the autoantibodypositive children before seroconversion than in the corresponding time intervals in controls (0.43 mg/l; 95% CI 0.29-0.56 vs 0.22 mg/l; 95% CI 0.10-0.34 mg/l; P!0.01). Children carrying the high-risk HLA genotype had lower plasma IGF1 and IGFBP3 concentrations at the age of 24 months than those with low-risk genotypes (P!0.05 and ! 0.01 respectively). Conclusions: Circulating IGF1 and IGFBP3 appear to have a role in early development of b-cell autoimmunity. The decreased IGF1 concentrations in children with the high-risk HLA genotype may contribute to the reduced growth previously described in such children.

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“…Although the present study offers limited information, increased IGF-1/insulin signaling and induced food intake both appear as independent, overlapping effects. IGF-1 plays a vital role in the regulation of somatic growth and cellular proliferation, and may be used as a measure of GH bioactivity by accurately reflecting the GH secretory status [27]. Fig.…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone Administration Controls Body Composition Associated with Changes of Thermogenesis in Obese KK-Ay Mice~!2009-08-29~!2010-01-12~!2010-03-26~!

Hioki¹,

Yoshida²,

Kogure³

et al. 2010

TOEJ

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Abstract:We investigate the effects of continuous human growth hormone (GH) therapy in young obese mice on thermogenesis. Female KK-A y obese mice (n=10) were injected subcutaneously with GH (3.5 mg/kg/day) for 30 days from 42 days old. As a control, physiological saline was administered (n=10). At the terminal point (71 days old), GH administration affected linear growth, and the Lee obesity index (3 square root body weight/nasoanal length 1000) was significantly decreased. Rates of inguinal and perimetric white adipose pads per body weight also decreased. Free fatty acid levels decreased, while plasma insulin concentrations and homeostasis model assessment insulin resistance were increased (P<0.01). Plasma insulin-like growth factor (IGF-1) levels markedly rose (P<0.00001). Uncoupling protein1 (UCP1) and UCP3 mRNA expressions in brown adipose tissue were inhibited (P<0.05). Continuous GH therapy changed obese body composition toward lean, however, the consequence could be the negative regulation of thermogenesis.

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Free insulin-like growth factors – measurements and relationships to growth hormone secretion and glucose homeostasis

Cited by 307 publications

References 352 publications

Changes in bioactive IGF-I and IGF-binding protein-1 during an oral glucose tolerance test in patients with liver cirrhosis

Changes in bioactive IGF-I and IGF-binding protein-1 during an oral glucose tolerance test in patients with liver cirrhosis

Circulating IGF1 and IGFBP3 in relation to the development of β-cell autoimmunity in young children

Growth Hormone Administration Controls Body Composition Associated with Changes of Thermogenesis in Obese KK-Ay Mice~!2009-08-29~!2010-01-12~!2010-03-26~!

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