Cold Exposure Alleviates T2DM Through Plasma-Derived Extracellular Vesicles.

Area of Science:

• Metabolic disease research
• Environmental physiology
• Cellular and molecular biology

Background:

• Cold exposure, including winter swimming and cold water immersion, is anecdotally linked to health benefits.
• Emerging evidence suggests cold exposure may influence metabolic processes and potentially alleviate type 2 diabetes (T2DM).
• Systemic cold temperature (CT) exposure may impact blood components and systemic physiology.

Purpose of the Study:

• To investigate the effects of chronic cold exposure on T2DM mice.
• To explore how cold exposure mitigates the incidence and progression of T2DM.
• To elucidate the underlying mechanisms of cold exposure's impact on glucose metabolism and insulin sensitivity.

Main Methods:

• T2DM mice were exposed to cold temperature (CT, 4-8°C) or room temperature (RT, 22-25°C).
• Blood and organ specimens underwent biochemical testing, ELISA, HE staining, and immunofluorescence.
• Glucose uptake, signaling pathways (AKT, IRS1), and islet cell apoptosis were assessed using flow cytometry and Western blot.

Main Results:

• CT and CT mice plasma-derived extracellular vesicles (CT-EVs) reduced blood glucose and improved insulin sensitivity in T2DM mice.
• CT-EVs enhanced glucose metabolism, insulin secretion, and glycogen accumulation, while protecting islets from streptozotocin-induced destruction.
• CT-EVs increased p-IRS1 and p-AKT expression in adipocytes and hepatocytes, demonstrating a pro-insulin sensitivity effect.

Conclusions:

• Cold exposure, primarily through plasma-derived EVs, exhibits anti-diabetic effects beneficial for T2DM.
• This mechanism offers a potential explanation for lower diabetes prevalence in colder climates.
• Cold-stimulated plasma EVs represent a promising therapeutic strategy for T2DM.