Insulin Regulates the Serum Levels of Low Molecular Weight Insulin-Like Growth Factor-Binding Protein*

Abstract

The serum levels of 34K insulin-like growth factor (IGF)-binding protein were measured by RIA in 88 type 1 diabetic patients, 9 patients with type 2 diabetes, 7 patients with insulinoma, 19 normal subjects (all after an overnight fast), and 82 normal subjects after a breakfast meal. In addition, the effect of 2- to 3-h euglycemic steady state hyperinsulinemia on serum IGF-binding protein and IGF-1 levels was studied in some subjects in each of the fasted groups. Compared with normal subjects, the mean serum IGF-binding protein levels were 4-fold (P less than 0.001) higher in type I diabetic patients treated with conventional insulin injections, 2.5-fold (P less than 0.001) higher in those treated with continuous sc insulin infusion, and 2-fold (P less than 0.05) higher in patients with type 2 diabetes. In the patients with insulinoma, the mean IGF-binding protein level was 63% below normal (P less than 0.001), and it normalized after removal of the tumor. There was a slight negative correlation between the IGF-binding protein level and insulin dose in the diabetic patients (r = -0.22; P less than 0.05). In normal subjects, serum insulin concentrations were 2-fold higher (P less than 0.001) and the IGF-binding protein level was 29% lower after a meal (P less than 0.05) than in the fasting state. Serum IGF-I concentrations were virtually identical in the type 1 and 2 diabetic patients, insulinoma patients, and normal subjects. During steady state euglycemic hyperinsulinemia, the IGF-binding protein level fell by 40-70% in each group (P less than 0.001), whereas the IGF-I level declined (P less than 0.05) in the type 2 diabetic patients only. The decline of binding protein was closely related to the baseline level (r = 0.94; P less than 0.001). No correlation was found between serum IGF-I and binding protein levels in any group. In conclusion, 1) serum 34K IGF-binding protein levels are elevated in type 1 and 2 diabetic patients and decreased in patients with insulinoma; 2) the serum binding protein, but not IGF-I concentration is decreased by acute hyperinsulinemia; and 3) these data suggest that the serum insulin concentration plays a role in regulation of the serum 34K IGF-binding protein concentration.

Relationship of Dietary Protein and Soy Isoflavones to Serum IGF-1 and IGF Binding Proteins in the Prostate Cancer Lifestyle Trial

“…This is encouraging, as fasting insulin has been associated with increased risk of prostate cancer (41). As expected, fasting insulin was inversely correlated to IGFBP-1 395 at baseline and changes in fasting insulin were negatively associated to changes in IGFBP-1 at 1 yr (42).…”

Globulina ligadora dos hormônios sexuais e proteína ligadora 1 do IGF-1: marcadores para resistência à insulina na pubarca precoce?

“…Adicionalmente, tanto a insulina como o fator de crescimento 1 semelhante à insulina (IGF-1) são capazes de estimular a produção de androgênios pelas células da teca e intersticial dos ovários assim como aumentar a esteroidogênese e a responsividade ao ACTH de células adrenocorticais humanas em cultura (17,18). A insulina também modula a ação do IGF-1 e da IGFBP-1 e inibe a produção da SHBG em linhagens de células do hepatoma humano (19). Adicionalmente, tem sido demonstrado que em mulheres hiperandrogênicas a diminuição dos níveis de insulina através de agentes sensibilizadores da insulina reduz os níveis séricos dos androgênios, aumenta a concentração da SHBG e restaura a ovulação e os ciclos menstruais, provavelmente através da redução da atividade do citocromo P450c17α ovariano (20).…”

Macrosomia and the IGF System: A Short Review

“…IGF-1 in the umbilical cord correlates well with fetal and placental weight. IGF-1 and -2 on the fetal side of placenta are primarily regulated by the IGFBP-1, which is GH independent, binds IGF-1 more reluctantly than IGFBP-3 and is influenced by insulin in diabetic and non-diabetic subjects [56]. This further emphasizes that the same elements work differently on the maternal and fetal side.…”