Insulin-Like Growth Factor Dynamics in Metabolic Disorders

The insulin-like growth factor (IGF) axis comprises IGF-1 and IGF-2 hormones that share structural homology with insulin and engage IGF-1 and insulin receptor isoforms to regulate glucose uptake, lipid metabolism and cellular growth. Circulating IGFs are bound and modulated by a family of high-affinity IGF binding proteins (IGFBPs), which govern ligand half-life, tissue distribution and receptor access. In obesity and type 2 diabetes, hyperinsulinaemia and chronic low-grade inflammation disrupt normal feedback loops, leading to altered IGFBP-1 and IGFBP-2 levels, inappropriate free IGF-1 availability and tissue-specific resistance. Paracrine IGF-1 signalling within the vascular endothelium and adipose depots drives depot-specific adipose remodelling, influences energy expenditure and contributes to ectopic fat deposition. Dysregulated IGF dynamics underpin insulin resistance, hepatic steatosis and vascular dysfunction, positioning components of the IGF axis as both biomarkers for disease progression and targets for therapeutic intervention in metabolic disorders worldwide.

Research from Nature Portfolio

Recent investigations have elucidated the paracrine influence of endothelial IGF-1 receptor expression on adipose tissue phenotype, demonstrating that targeted reduction of endothelial IGF-1R under high-fat feeding drives depot-specific white fat remodelling, boosts whole-body energy expenditure and enhances systemic insulin sensitivity via increased endothelial release of malonate. This work identifies malonate prodrugs as potential modulators of adipose–liver crosstalk and metabolic homeostasis. Foundational mechanistic studies have also revealed that the antidiabetic drug metformin stimulates hepatic expression of IGFBP-2 through an AMPK–Sirt1–PPARα cascade, thereby reducing IGF-1 receptor activation and ameliorating insulin resistance. These advances uncover novel nodes for therapeutic intervention within the IGF axis and underscore its role in orchestrating metabolic resilience.

Insulin-Like Growth Factor Dynamics in Metabolic Disorders publication trend

The graph below shows the total number of articles in insulin-like growth factor dynamics in metabolic disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Insulin-like growth factor (IGF): A hormone structurally related to insulin that regulates cell growth, glucose metabolism and survival through interaction with IGF receptors.

IGF binding proteins (IGFBPs): A family of six high-affinity proteins that bind IGFs, modulating their distribution, receptor access and circulating half-life.

Paracrine signalling: Local communication between adjacent cells via secreted factors that act on nearby targets rather than through systemic circulation.

AMPK–Sirt1–PPARα cascade: A metabolic regulatory pathway in which AMP-activated protein kinase (AMPK) and sirtuin 1 (Sirt1) activate peroxisome proliferator-activated receptor alpha (PPARα) to control gene expression related to energy homeostasis.

Adipose tissue remodelling: Structural and functional adaptation of fat depots through changes in cell size, number or extracellular matrix in response to nutritional and hormonal cues.

References

1. Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice. Nature Communications (2025).
2. Cross-species transcriptomics identifies obesity associated genes between human and mouse studies. Journal of Translational Medicine (2024).
3. IGF-1 and IGFBP-1 as Possible Predictors of Response to Lifestyle Intervention—Results from Randomized Controlled Trials. International Journal of Molecular Sciences (2024).
4. Adiponectin, IGFBP-1 and -2 are independent predictors in forecasting prediabetes and type 2 diabetes. Frontiers in Endocrinology (2023).
5. The insulin like growth factor and binding protein family: Novel therapeutic targets in obesity & diabetes. Molecular Metabolism (2018).
6. Metformin stimulates IGFBP-2 gene expression through PPARalpha in diabetic states. Scientific Reports (2016).