The role of the incretin GIP in inflammation

TL;DR

This review explores how the hormone GIP influences inflammation, highlighting its potential as a target for treating metabolic and inflammatory diseases.

Contribution

The paper systematically reviews the emerging role of GIP in inflammation and its potential as a therapeutic target in immunometabolism.

Findings

GIP exhibits both pro- and anti-inflammatory effects depending on the tissue and metabolic context.

Pharmacological targeting of the GIP receptor shows promise in modulating inflammatory processes.

Dual agonists of GIP and GLP-1 improve metabolic and inflammatory outcomes, but their individual roles remain unclear.

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone traditionally known for its insulinotropic and adipogenic effects. However, its role in immune modulation and inflammation has recently gained attention, particularly in the context of metabolic diseases. By conducting a comprehensive search into the scientific literature since the discovery of GIP hormone, this review examines the biological evidences linking GIP and inflammation in pre-clinical and clinical studies. Pharmacological approaches targeting the GIP receptor (GIPR) with effects on inflammatory processes are discussed as well, including the latest GIP-based multi-target approaches. The impact of GIP on inflammation appears context-dependent and influenced by tissue-specific receptor expression and metabolic status. While GIP has been shown to exert both pro- and anti-inflammatory effects in experimental models, clinical data are still limited. The success of GIP/glucagon-like peptide-1 (GLP-1) dual agonists in improving glycometabolic and inflammatory outcomes, highlighted the need to disentangle the individual contributions of each pathway. GIPR remains a promising, yet understudied, target in immunometabolism. Future studies are needed to clarify the molecular mechanisms underpinning GIP’s immunomodulatory actions and evaluate the anti-inflammatory potential of GIP-targeting therapies in clinical settings.

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