Adenosine as a modulator of human islet function and hypoxic tolerance

Area of Science:

• Cellular and Molecular Biology
• Endocrinology
• Regenerative Medicine

Background:

• Islet transplantation is a promising therapy for type 1 diabetes.
• Early graft loss due to hypoxia limits transplant effectiveness.
• Reducing cellular metabolic demand is a potential strategy to improve islet resilience.

Purpose of the Study:

• To evaluate the impact of adenosine (AD) on human islet (HI) viability, function, and metabolic suppression under hypoxic stress.
• To determine if AD preconditioning can enhance hypoxia tolerance in HI.

Main Methods:

• Human islets were exposed to hypoxic conditions (1% O2) with and without 1 mM adenosine (AD).
• Islet viability, insulin content, and glucose-stimulated insulin secretion were assessed.
• Reversibility of AD effects and protective effects of AD preconditioning were evaluated.

Main Results:

• 1 mM AD induced a transient reduction in insulin content, reversible within 96 hours, without affecting viability or function.
• AD preconditioning preserved HI viability and glucose-stimulated insulin secretion after 48-hour hypoxia.
• AD preconditioning mitigated functional losses post-reperfusion.

Conclusions:

• Adenosine preconditioning is an effective and reversible method to reduce islet metabolic demand and enhance hypoxia tolerance.
• AD offers a novel strategy to mitigate ischemia-reperfusion injury in islet transplantation.
• AD can be integrated into various stages of beta-cell replacement workflows for improved cell-based therapies.