Diffusion into human islets is limited to molecules below 10 kDa

Area of Science:

• Endocrinology
• Cell Biology
• Biomedical Engineering

Background:

• Isolated islets are crucial for diabetes research and type 1 diabetes transplantation.
• A significant diffusion barrier within islets leads to core cell death.
• Previous studies relied on theoretical models, lacking direct measurement of islet diffusion rates.

Purpose of the Study:

• To directly measure the diffusion barrier in intact human islets.
• To determine the barrier's impact on insulin secretion.
• To investigate methods for overcoming the diffusion barrier.

Main Methods:

• Utilized fluorescent dextran beads (0.9-70 kDa) to assess diffusion into islets.
• Monitored diffusion of 2-NBDG (a fluorescent glucose analog).
• Assessed cell viability and insulin secretion after papain/0 Ca(2+) treatment to reduce the diffusion barrier.

Main Results:

• Dextran beads > 0.9 kDa could not penetrate the islet core, indicating a significant diffusion barrier.
• Intra-islet diffusion rate was measured at 1.5 ± 0.2 μm/min for 2-NBDG.
• Reducing the diffusion barrier improved islet cell viability and insulin release, particularly in low glucose.
• Glucose-stimulated insulin secretion in large islets remained impaired despite barrier reduction.

Conclusions:

• The islet diffusion barrier is a primary cause of core cell death and poor survival in larger isolated islets.
• While reducing the barrier enhances cell viability, it does not solely explain or resolve impaired glucose-stimulated insulin secretion in large islets.