(Poly)phenols and diabetes: From effects to mechanisms by systematic multigenomic analysis

Area of Science:

• Metabolic diseases
• Nutrigenomics
• Bioinformatics

Background:

• Diabetes mellitus is a growing global health concern, marked by pancreatic beta-cell dysfunction and insulin deficiency.
• Polyphenols, natural compounds, exhibit beneficial effects in diabetes management through diverse cellular actions, including glucose homeostasis.
• The precise mechanisms of action for (poly)phenol metabolites in diabetes remain largely unexplored.

Purpose of the Study:

• To investigate the multigenomic effects of (poly)phenols and their metabolites.
• To identify regulatory networks and mechanisms associated with diabetes management.
• To explore the potential of these compounds in nutraceutical and pharmaceutical applications for diabetes.

Main Methods:

• Integration of published studies on gene expression changes induced by (poly)phenols in diabetes models (human, animal, cell lines).
• Bioinformatic analysis to identify differentially expressed genes and regulatory factors.
• In silico 3D docking to predict interactions between metabolites and key transcription factors.

Main Results:

• Identified key cell signaling pathways (FoxO, AMPK, p53), endocrine resistance, immune responses, apoptosis, and senescence as modulated targets.
• Discovered potential interactions between specific (poly)phenol metabolites and transcription factors (FOXO1, PPARG, SIRT1, MAFA).
• Apigenin, luteolin, and naringenin glucuronide demonstrated significant binding affinity to SIRT1.

Conclusions:

• (Poly)phenol metabolites possess the potential to modulate critical pathways involved in diabetes.
• These findings support the development of nutraceuticals and pharmaceuticals for diabetes management.
• Targeting these molecular mechanisms offers a promising strategy for addressing age-related diabetes incidence.