scholarly journals Dietary intake and the insulin-like growth factor system: effects of migration in two related populations in India and Britain with markedly different dietary intake

2005 ◽  
Vol 8 (6) ◽  
pp. 620-627 ◽  
Author(s):  
AH Heald ◽  
R Sharma ◽  
SG Anderson ◽  
A Vyas ◽  
K Siddals ◽  
...  

AbstractBackgroundThe insulin-like growth factor (IGF) system is implicated in the pathogenesis of diabetes and cardiovascular disease.ObjectiveWe report the effects of total energy intake on the IGF system in two populations with markedly different dietary macronutrient intake and cardiovascular event rate.Design, subjects and settingDietary macronutrient intake was measured in a specific Gujarati migrant community in Sandwell, UK (n = 205) compared with people still resident in the same villages of origin in India (n = 246). Fasting IGF-I, IGF-binding protein (IGFBP)-1 and IGFBP-3, insulin and glucose (0 and 2-hour) were measured.ResultsTotal energy and total fat intake were higher in UK migrants, as were IGFBP-3 and IGF-I (mean (95% confidence interval): 145.9 (138.1–153.6) vs. 100.9 (94.6–107.3) ng ml-1; F = 76.6, P < 0.001). IGFBP-1 was lower in UK migrants (29.5 (25.9–33.0) vs. 56.5 (50.6–62.5) μg l-1; F = 48.4, P < 0.001). At both sites, IGF-I correlated positively with total energy (Spearman's ρ = 0.45, P < 0.001) and total fat (ρ = 0.44, P < 0.001) as did IGFBP-3 with total energy (ρ = 0.21, P < 0.05) and fat (ρ = 0.26, P < 0.001). Conversely, in Indian Gujaratis, IGFBP-1 fell with increasing total energy (ρ = -0.27, P < 0.001) and fat intake (ρ = -0.26, P < 0.01) but not in UK Gujaratis. Multiple linear regression modelling showed that increasing quartiles of fat intake were associated with higher IGF-I (β = 0.42, P = 0.007) independent of age, body mass index, plasma insulin, fatty acids and 2-hour glucose.ConclusionIn these genetically similar groups, migration to the UK and adoption of a different diet is associated with marked changes in the IGF system, suggesting that environmental factors profoundly modulate serum concentrations and actions of IGFs.

2002 ◽  
Vol 93 (5) ◽  
pp. 1669-1675 ◽  
Author(s):  
Lars Rosendal ◽  
Henning Langberg ◽  
Allan Flyvbjerg ◽  
Jan Frystyk ◽  
Hans Ørskov ◽  
...  

The influence of initial training status on the response of circulating insulin-like growth factor (IGF) and its binding proteins (IGFBP) to prolonged physical training was studied in young men. It was hypothesized that highly standardized training would result in more extensive changes in the circulating IGF system in untrained subjects because of lower fitness level. Seven untrained (UT) and 12 well-trained (WT) individuals performed 11 wk of intense physical training (2–4 h daily). Fasting serum samples were analyzed for total and free IGF-I and -II, for IGFBP-1 to -4, as well as for IGFBP-3 proteolysis. Eleven weeks of physical training resulted in decreased levels of total IGF-I, free IGF-I, and IGFBP-4 in both the UT and WT groups. In the UT group, IGFBP-2 increased, IGFBP-3 decreased [from 4,255 ± 410 (baseline) to 3,896 ± 465 (SD) μg/l ( week 4); P < 0.05], and IGFBP-3 proteolysis increased [from 28 ± 8% (baseline) to 37 ± 7% ( week 4) and 39 ± 12% ( week 11); P < 0.05], whereas no significant changes were found in the WT group. In conclusion, intense physical training results in a marked influence on the IGF system and its binding proteins with generally more extensive changes seen in the untrained individuals. Also, prolonged physical training resulted in increased IGFBP-3 proteolysis in previously untrained individuals only, indicating that intense physical training affects trained and untrained individuals differently.


Reproduction ◽  
2000 ◽  
pp. 407-416 ◽  
Author(s):  
TS Gadd ◽  
RP Aitken ◽  
JM Wallace ◽  
DC Wathes

The aim of the present study was to investigate the effects of administering a high plane diet during early to mid-gestation on the uterine and placental insulin-like growth factor (IGF) system and on systemic IGF-I concentrations in pregnant adolescent ewes with restricted placental growth. Embryos recovered from superovulated ewes inseminated by a single sire were transferred in singleton to the uterus of adolescent recipients. After transfer ewes were offered a high (H) or moderate (M) amount of a complete diet calculated to promote rapid or normal maternal growth rates, respectively. Five ewes from each group were switched from either M to H or H to M diets at day 52 of gestation. Maternal and fetal blood samples and placental tissues were collected from all animals at day 104. Ewes on the high plane diet from mid-gestation (HH, MH groups) had restricted placental mass (P < 0.01) and tended to have smaller fetuses. This was associated with increased maternal plasma IGF-I concentrations (P < 0.001). The pattern of expression of components of the IGF system in the uterus and placenta was studied by in situ hybridization. IGF-I mRNA concentrations were below the limit of detection. IGF-II mRNA expression was high in the fetal mesoderm and present in maternal stroma, but was not influenced by nutritional treatment. In contrast, IGF binding protein 1 (IGFBP-1) mRNA expression was higher (P < 0.05) and IGFBP-3 mRNA expression was lower (P < 0.05) in the endometrial glands of ewes in HH and MH groups. In the fetal trophoblast, IGFBP-3 mRNA expression was higher in the MH group. Type 1 IGF receptor expression was increased (P < 0. 01) in the luminal epithelium of the HM group and IGFBP-2 mRNA expression was highest in the placentome capsule of ewes in the HH group. Together, these results indicate that reprogramming of the uterine and placental IGF axis by maternal nutrition could contribute to placental growth retardation in growing adolescent sheep.


2000 ◽  
Vol 165 (3) ◽  
pp. 545-556 ◽  
Author(s):  
EJ Whellams ◽  
LA Maile ◽  
JK Fernihough ◽  
ME Billingham ◽  
JM Holly

Increased concentrations of insulin-like growth factor (IGF) system components have previously been observed in rheumatoid arthritis (RA) and osteoarthritis (OA); however, disruption of the IGF axis and the implications for the disease process remain largely unaddressed. This study was undertaken to characterise the IGF binding protein (IGFBP)-3 proteolysis and complex formation systems in synovial fluid and to investigate changes in these systems in arthritic disease, and their impact on the availability of IGF. Western blotting or autoradiography of SDS gels was used to visualise IGFBP-3 or its proteolysis. IGF-I and IGFBP-3 concentrations were determined by radioimmunoassays and acid-labile subunit (ALS) was measured by ELISA. A shift in distribution of IGFBP-3 and IGF-I in RA and OA synovial fluids (RASynF, OASynF) and an associated increase in ALS suggested the presence of 150 kDa ternary complexes. IGFBP-3 proteolysis was decreased in RASynF and OASynF, but was apparent in size-fractionated fluid and resembled serum activity. The presence of serum-like inhibitors of IGFBP-3 proteolysis in RASynF was also demonstrated by the ability of this fluid, and 150 kDa fractions from its size fractionation, to inhibit IGFBP-3 proteolysis in the other synovial fluid. A marked disruption in the IGF system was observed, as considerably more IGF-I was retained in ternary complexes. We also classified the IGFBP-3 proteolysis system in synovial fluid and found it to be disturbed in RASynF and OASynF. These changes may be caused by an increased flux of circulatory proteins into synovial fluid, resulting from an inflammation-induced increase in vascular permeability. The net result in RA and OA would be a decrease in IGF availability in arthritic joints, and therefore loss of a potential anabolic stimulus. This disruption to the IGF axis would influence disease progression in RA and OA.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4292-4292
Author(s):  
Kristin Dawczynski ◽  
Bernd Gruhn ◽  
Nadine Pfaffendorf ◽  
Wittig Susan ◽  
Astrit Voigt ◽  
...  

Abstract Insulin-like growth factor (IGF) system plays an important role in regulating cellular proliferation. Alterations to the Insulin-like growth factor system have been reported for different tumors. They are of particular interest in the search for new prognostic and therapeutic approaches to cancer treatment. This study aimed to investigate the expression of IGFBP-2, IGFBP-3, IGF-I and IGF-II genes in leukemic cells from children with previously untreated acute myeloblastic leukemia (AML).The expression of IGF-I and IGF-II genes as well as IGFBP-2 and IGFBP-3 genes were measured using TaqMan real-time PCR in 50 children (mean age 10.8±4.8 years). All four genes were expressed with a great variability. RNA samples were extracted from leukemic cells enriched by Ficoll-Hypaque density gradient separation of bone marrow or peripheral blood mononuclear cells (MNC). MNC samples from peripheral blood and bone marrow of healthy children were used as controls. The median expression of IGFBP-2 was 25 times higher in AML cells than in peripheral MNC (p<0.001) and 10 times higher in bone marrow of healthy children (p<0.01). Increased IGFBP-2 gene expression at time of diagnosis was associated with a poor prognosis and a shortened survival time. Leukemic cells of patients who remained in continuous complete remission during the follow up showed a significant decreased IGFBP-2 gene expression at time of diagnosis compared to patients who suffered from relapse (p=0.05).On the other hand, AML cells showed a significantly lower IGFBP-3 gene expression than controls. The median expression of IGFBP-3 was 30 times lower in AML cells than in peripheral MNC (p<0.001) and 20 times lower than in bone marrow of healthy children (p<0.001). No significant difference could be found in IGF-I and IGF-II expression between leukemic and normal cells. Leukemic cells from children with previously untreated AML express components of IGF system. Especially IGFBP-2 seems to play an important role. By this mechanism, IGFBP-2 promotes their own growth in an autocrine, paracrine or endocrine manner. Whether these components will be useful as prognostic factors in stratification of AML treatment in children needs to be evaluated.


2003 ◽  
Vol 6 (2) ◽  
pp. 175-180 ◽  
Author(s):  
AH Heald ◽  
JE Cade ◽  
JK Cruickshank ◽  
S Anderson ◽  
A White ◽  
...  

AbstractObjective:The insulin-like growth factor (IGF) system has been implicated in the aetiopathogenesis of cancer, cardiovascular disease and diabetes. Since dietary factors and ethnicity are considered contributory to the development of these diseases, we examined the IGF system in relation to nutritional intake by ethnic group.Design, subjects and setting:Dietary intake in 257 subjects of White European, African-Caribbean and Pakistani ethnic origin living in Manchester, UK was assessed using ethnic-group-specific food-frequency questionnaires to assess habitual nutrient intake over the previous 12 months. Fasting IGF-I, IGF-II and IGF-binding protein-1 (IGFBP-1) concentrations were determined and their relationship to specific dietary constituents was analysed.Results:Analysis by quintiles of nutrient intake showed a significant increase in circulating IGF-I concentration with increasing dietary fat intake (F for trend = 3.9, P < 0.01), saturated fat intake (F = 3.3, P = 0.01) and for protein intake (F = 4.2, P < 0.01). There was also a significant increase in IGF-II by quintiles of dietary protein intake (F = 2.7, P < 0.05). There was a trend for increasing IGF-I with increasing energy intake. The relationships between circulating concentration of IGFBP-1, an acute regulator of IGF action, and fat/protein intake were opposite to those for IGF-I and IGF-II. Multiple linear regression modelling showed that people of Pakistani origin and older subjects had lower levels of IGF-I (Pakistani origin vs. others, P < 0.001) (age, P < 0.001 for both). There was an independent inverse relationship between IGF-I and dietary carbohydrate intake (P = 0.036).Conclusions:This study provides evidence for a dietary contribution to regulation of the IGF system, although the effects of ethnicity on circulating IGF levels remain dominant. We propose that the IGF system's influences on cancer risk in specific ethnic groups are potentially modifiable by dietary intervention.


2006 ◽  
Vol 16 (2) ◽  
pp. 86-92 ◽  
Author(s):  
Tiffany G. Harris ◽  
Howard D. Strickler ◽  
Herbert Yu ◽  
Michael N. Pollak ◽  
E. Scott Monrad ◽  
...  

1993 ◽  
Vol 136 (1) ◽  
pp. 91-104 ◽  
Author(s):  
L. R. Donahue ◽  
W. G. Beamer

ABSTRACT Although GH is known to regulate somatic growth during development, its role in regulating adult body composition is less well defined. The effects of GH on individual body compartments – water, fat, protein and mineral – are achieved both by the action of GH and by a GH-induced hormone, insulin-like growth factor-I (IGF-I). We used a genetic model of GH deficiency, the 'little' (gene symbol lit) mouse, to determine the GH regulation of IGF-I and its insulin-like growth factor-binding proteins (IGFBPs) and to define the interaction between these hormones and each body compartment in adults. Our results showed that GH-deficient lit/lit mice had reduced levels of serum IGF-I (range 38–130 μg/l) compared with normal lit/+ littermates (range 432–567 μg/l) between 2 and 52 weeks of age. The lit/lit mice did not experience the fivefold increase in IGF-I between 2 and 4 weeks of age that was seen in lit/+ mice. In lit/lit serum, overall binding of 125I-labelled IGF-I to the four IGFBPs was reduced, solely in response to a reduced amount of IGFBP-3. No overall differences were found between lit/lit and lit/+ mice in the binding of 125I-labelled IGF-I to IGFBP-2, -1 or -4. Age-related declines in IGF-I and IGFBPs were seen in lit/lit mice. However, adult levels of IGF-I were maintained in lit/+ mice to at least 52 weeks of age, as were levels of IGFBP-1 and -4, while IGFBP-3 and -2 declined with age. With respect to body composition, comparison of lit/lit with lit/+ mice showed that the lit/lit mice were characterized by abnormally large adipose tissue stores and reduced body water, protein and mineral from 2 weeks onward. These changes occurred despite normal energy intake in lit/lit mice up to 52 weeks of age, indicating that neither undernutrition nor hyperphagia is characteristic of this GH-induced model of obesity. Furthermore, lit/lit males accrued more body fat beginning at an earlier age than lit/lit females. With advancing age, the per cent body fat increased in both lit/lit and lit/+ mice, while the per cent body water and mineral declined. In lit/lit but not lit/+ mice, per cent protein also declined with age. The changes in body water and fat are attributable to lack of adequate GH in the genetically GH-deficient lit/lit mouse. On the other hand, the changes in body protein are more likely to be effects of IGF-I. Changes in mineral observed in lit/lit mice could be the result of action by GH, IGF-I or both hormones. Therefore, when GH is chronically manipulated by GH deficiency as in lit/lit mice, by GH excess as in acromegaly, or by GH therapy, all four body compartments are affected, suggesting that GH therapy is most valuable when the treatment goal is to alter overall body composition. Journal of Endocrinology (1993) 136, 91–104


2007 ◽  
Vol 92 (9) ◽  
pp. 3660-3666 ◽  
Author(s):  
Iona Cheng ◽  
Katherine DeLellis Henderson ◽  
Christopher A. Haiman ◽  
Laurence N. Kolonel ◽  
Brian E. Henderson ◽  
...  

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