D-Mannose Alleviates Type 2 Diabetes and Rescues Multi-Organ Deteriorations by Controlling Release of Pathological...

Area of Science:

• Metabolic disease research
• Endocrinology
• Pharmacology

Background:

• Type 2 diabetes (T2D) is a widespread metabolic disease lacking a cure.
• Extracellular vesicles (EVs) play a critical role in T2D pathogenesis by mediating insulin resistance and metabolic dysfunction.
• Current pharmaceutical options for controlling pathological EV release in T2D are limited.

Purpose of the Study:

• To investigate the therapeutic potential of D-mannose in a mouse model of T2D.
• To elucidate the mechanisms by which D-mannose impacts T2D pathology, particularly concerning EVs and organ function.

Main Methods:

• Utilized the db/db mouse model for T2D.
• Administered D-mannose orally.
• Assessed diabetic symptoms, liver function, insulin resistance, gut microbiome, T lymphocytes, and bone density.
• Investigated the effect of D-mannose on macrophage-derived EVs and CD36 expression in hepatocytes.

Main Results:

• Oral D-mannose administration safely ameliorated T2D symptoms in db/db mice.
• D-mannose accumulated in the liver, alleviating hepatic steatosis and improving insulin resistance.
• D-mannose reduced pathological EVs from macrophages by inhibiting CD36 expression, restoring hepatocyte function.
• D-mannose administration also conferred extra-hepatic benefits, including retarding diabetic bone loss.

Conclusions:

• D-mannose emerges as a potential therapeutic candidate for T2D.
• This study highlights the role of sugars in regulating intercellular EV communication.
• D-mannose offers a novel therapeutic avenue for T2D by targeting EV crosstalk and mitigating multi-organ complications.