Medical science monitor : international medical journal of experimental and clinical researchOct 27, 2026

Thermosensitive Ion Channels and Their Possible Role in Diabetes and Treatment

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 28, 2026

Abstract

Thermosensitive transient receptor potential (TRP) channels are linked to immune and metabolic regulation in diabetes mellitus (DM).

Low-grade inflammation and metabolic stress in DM may impact calcium signaling and contribute to insulin resistance.
Cell-based and animal studies indicate that TRP-mediated calcium influx may interact with key signaling pathways involved in inflammation and metabolism.
TRPV1 and TRPV4 are associated with processes like inflammation, neuroimmune signaling, and vascular dysfunction.
TRPM8 is linked to cold sensing and could play a role in anti-inflammatory metabolic changes.
TRPA1 is related to oxidative stress and sensory signaling.
Current temperature-based interventions and natural compounds targeting TRP channels are mostly in the preclinical stage, with limited evidence in human studies.

Simplified

Environmental temperature can influence immune and metabolic homeostasis partly through thermosensitive transient receptor potential (TRP) channels. In diabetes mellitus (DM), low-grade inflammation, metabolic stress, and altered calcium signaling contribute to insulin resistance, ß-cell dysfunction, neuropathy, vascular dysfunction, and tissue remodeling. This narrative review summarizes evidence linking thermosensitive and stress-sensitive TRP channels, especially transient receptor potential vanilloid 1 (TRPV1), transient receptor potential vanilloid 4 (TRPV4), transient receptor potential melastatin 8 (TRPM8), and transient receptor potential ankyrin 1 (TRPA1), with immunometabolic regulation in DM. Cell-based and animal studies suggest that TRP-mediated calcium influx can interact with nuclear factor kappa B, AMP-activated protein kinase/mechanistic target of rapamycin, and reactive oxygen species/NLRP3 inflammasome signaling. TRPV1 and TRPV4 are predominantly associated with inflammatory amplification, neuroimmune signaling, endothelial dysfunction, and fibrosis, whereas TRPM8 is associated with cold sensing, thermogenesis, and anti-inflammatory metabolic remodeling. TRPA1 is associated with oxidative stress, electrophilic sensing, sensory transduction, and nociception. Temperature-based interventions, natural compounds, and nano-targeted systems remain promising but largely preclinical approaches, and TRP-specific causality has not been fully established in human cohorts. This article aims to review the roles of thermosensitive TRP channels in DM and their potential as therapeutic targets.

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Thermosensitive Ion Channels and Their Possible Role in Diabetes and Treatment

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