Potential Role of Insulin Growth-Factor-Binding Protein 2 as Therapeutic Target for Obesity-Related Insulin Resistance
Abstract
:1. Introduction
2. Building the Molecular Structure of IGFBP2
3. Mechanism of Action of IGFBP2 and its Physiological Role
4. IGFBP2 and Obesity-Related Insulin Resistance
4.1. The Suggested Role of IGFBP2 in the Development of Obesity
4.2. The Mechanisms of IGFBP2 in Insulin Sensitivity
4.3. The Association of IGFBP2 and Type 2 Diabetes
4.4. IGFBP2 Is Associated with Metabolic Syndrome
4.5. Proposed Mechanisms of IGFBP2 in Obesity-Related Insulin Resistance
5. Diverse Strategies to Modify Serum IGFBP2 in a Prevention Context
5.1. Diet and Lifestyle Modifications
5.2. The Effect of Physical Activity on Serum IGFBP2
5.3. Epigenetic Regulation also Influences IGFBP2
6. Preclinical Pharmacology Studies of IGFBP2
7. Concluding Remarks and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
p53 | transformation-related protein 53 |
NFIA | nuclear factor IA |
PPRE | peroxisome-proliferator activated receptor responsive element |
E-Box | enhancer box |
bHLH | Basic helix-loop-helix |
EGFR1 | epidermal growth factor receptor 1 |
Sp1 | specificity protein 1 |
IGF1 | insulin growth factor type 1 |
HBD1 | heparin binding domain 1 |
NLS | nuclear localization sequence; |
HBD2 | heparin binding domain |
RGD | tripeptide Arg-Gly-Asp |
PDB | Protein data bank |
IGFBP2 | insulin growth factor binding protein 2. |
IGF2 | Insulin growth factor 2; |
IGF2R | Insulin growth factor receptor type 2 |
IGF1R | Insulin growth factor receptor type 1 |
Shc | SHC Adaptor Protein |
SOS | Son of Sevenless |
Ras | rat sarcoma |
Grb2 | growth factor receptor-bound protein 2 |
IRS1 | Insulin receptor substrate 1 |
PI3K | phosphatidylinositol 3-kinase |
PIP2 | Phosphatidylinositol 4,5-bisphosphate |
PIP3 | Phosphatidylinositol 3,4,5-trisphosphate |
GLU4 | glucose receptor type 4 |
MAPK | mitogen activated protein kinase |
RAF | Rapidly Accelerated Fibrosarcoma |
MEK | Mitogen-activated protein kinase kinase |
ERK | extracellular signal-regulated kinase |
PKC/CAMKII | protein kinase C/calcium/calmodulin dependent protein kinase II |
PDK | Pyruvate dehydrogenase kinase |
Akt | alpha serine/threonine-protein kinase |
RPTPβ | tyrosine phosphatase β |
PAPA1 | Pim-1-associated protein-1 |
P21 | cyclin-dependent kinase inhibitor 1 |
VEGF | vascular endothelial growth factor |
GSK3β | glycogen synthase kinase 3 β |
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Groups | Effectors | Effects of IGFBP2 | Physiological Context | Refs |
---|---|---|---|---|
Nutrients | Vitamin D | ↑ | Men with obesity with high vitamin D had increased IGFBP2 levels than lower vitamin D subjects | [84] |
Protein | ↓ | High protein diet was associated with decreased serum IGFBP2 levels | [81] | |
Calcium | ↓ | High calcium diet was associated with decreased serum IGFBP2 levels | [81] | |
Carbohydrates | ↑ | High carbohydrates diet was associated with increased serum IGFBP2 levels | [81] | |
Monounsaturated fat | ↑ | High monounsaturated diet was associated with increased serum IGFBP2 circulating levels | [81] | |
Lycopene and green tea | ↑ | A randomized, placebo-controlled, double-blinded crossover study showed that lycopene and green tea supplements were associated with increased serum IGFBP2 | [80] | |
Fruits and flavonoid intake | ↑ | High fruits and flavonoid intake was associated with increased serum IGFBP2 circulating | [83] | |
Growth factors | Insulin | ↑ | Insulin increased IGFBP2 in cultured embryonic kidney cell line | [85] |
IGF1, IGF2 and IGF analogues | ↑ | IGF1, IGF2 and IGF analogues increase IGFBP2 levels in human subjects and different cell models | [6,85,86,87,88,89,90] | |
Leptin | ↑ | Leptin stimulates expression of IGFBP2 and increases protein levels in human skeletal muscle cells | [52] | |
Physical activity | Endurance and resistance exercises | ↑ | Physical activity was associated with increased serum IGFBP2 | [91], [92] |
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Boughanem, H.; Yubero-Serrano, E.M.; López-Miranda, J.; Tinahones, F.J.; Macias-Gonzalez, M. Potential Role of Insulin Growth-Factor-Binding Protein 2 as Therapeutic Target for Obesity-Related Insulin Resistance. Int. J. Mol. Sci. 2021, 22, 1133. https://doi.org/10.3390/ijms22031133
Boughanem H, Yubero-Serrano EM, López-Miranda J, Tinahones FJ, Macias-Gonzalez M. Potential Role of Insulin Growth-Factor-Binding Protein 2 as Therapeutic Target for Obesity-Related Insulin Resistance. International Journal of Molecular Sciences. 2021; 22(3):1133. https://doi.org/10.3390/ijms22031133
Chicago/Turabian StyleBoughanem, Hatim, Elena M. Yubero-Serrano, José López-Miranda, Francisco J. Tinahones, and Manuel Macias-Gonzalez. 2021. "Potential Role of Insulin Growth-Factor-Binding Protein 2 as Therapeutic Target for Obesity-Related Insulin Resistance" International Journal of Molecular Sciences 22, no. 3: 1133. https://doi.org/10.3390/ijms22031133