Physiological parameters regulating circulating levels of the IGFBP-4/Stanniocalcin-2/PAPP-A axis
Grigorios Panagiotou1, Athanasios D Anastasilakis2, Georgios Kynigopoulos3
1Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Insights
This study identifies key factors influencing Insulin Growth Factor Binding Protein 4 (IGFBP-4), Stanniocalcin-2 (STC-2), and Pregnancy-Associated Plasma Protein-A (PAPP-A) levels in healthy individuals. Findings reveal associations with anthropometrics, diet, exercise, and diurnal rhythms.
Area of Science:
- Endocrinology
- Human Physiology
- Biochemistry
Background:
- Circulating levels of the Insulin Growth Factor Binding Protein 4 (IGFBP-4), Stanniocalcin-2 (STC-2), and Pregnancy-Associated Plasma Protein-A (PAPP-A) axis (ISPa) are implicated in various physiological functions.
- Predictors for these circulating levels remain largely uncharacterized in healthy human populations.
Purpose of the Study:
- To identify anthropometric and biochemical parameters associated with ISPa serum levels cross-sectionally.
- To investigate the day-night variation of ISPa.
- To examine ISPa regulation in response to mixed meal ingestion and aerobic exercise.
Main Methods:
- Cross-sectional evaluation of 122 healthy individuals.
- Subgroup analysis involving standardized mixed meal ingestion (125mL or 250mL) and 30-minute aerobic exercise.
- Day-night rhythm studies to assess diurnal variations.
- Measurement of total and intact IGFBP-4, STC-2, and PAPP-A serum levels.
Main Results:
- Serum total IGFBP-4 was predicted by PAPP-A and female gender. Intact IGFBP-4 correlated with creatinine. STC-2 levels were inversely associated with height and positively with female gender and body fat percentage.
- PAPP-A levels decreased post-meal, and total IGFBP-4 decreased after a 250mL meal. Exercise significantly increased STC-2 and PAPP-A levels.
- Intact and total IGFBP-4 exhibited a cortisol-like diurnal variation pattern.
Conclusions:
- This study provides novel insights into the anthropometric and physiological factors modulating ISPa serum levels in healthy humans.
- Identified predictors include gender, body composition, creatinine, and physiological stimuli like meals and exercise.
- The diurnal rhythm of IGFBP-4 is highlighted, suggesting complex regulatory mechanisms.
Background:
Insulin Growth Factor Binding Protein 4 (IGFBP-4), Stanniocalcin-2 (STC-2) and Pregnancy-Associated Plasma Protein-A (PAPP-A) have a well-documented involvement in several physiological functions in humans but predictors of their circulating levels remain largely unknown. We aimed to identify anthropometric and biochemical parameters associated with circulating levels of IGFBP-4/STC-2/PAPP-A axis (ISPa) cross-sectionally and to study their day-night variation and their regulation in response to mixed meal and exercise.
Methods:
One hundred twenty two healthy individuals were evaluated cross-sectionally. Subgroups were subjected to standardized mixed meal ingestion in increasing quantities of 125mL or 250mL, or aerobic exercise for 30min, or day-night rhythm study. Main outcome measurements were circulating IGFBP-4 (total and intact), STC-2 and PAPP-A levels.
Results:
In multivariate models, the main predictors of serum total IGFBP-4 were PAPP-A and female gender. Intact IGFBP-4 was positively associated with serum creatinine. Height was inversely and female gender and % of total body fat were positively correlated with STC-2. PAPP-A decreased after ingesting both the 125mL (p=0.03) and 250mL quantities (p=0.001), while total IGFBP-4 was reduced after the 250mL quantity (p=0.001). Exercise increased STC-2 and PAPP-A levels (p<0.001 for both). Intact, and to a lesser extent total, IGFBP-4 displayed a cortisol-like day/night variation.
Conclusions:
We report for the first time anthropometric and physiological modulators of ISPa serum levels in healthy humans.
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