Diffusion and polymerization determines the insulin absorption from subcutaneous tissue in diabetic patients

Area of Science:

• Pharmacology
• Endocrinology
• Physiology

Background:

• Subcutaneous absorption of short-acting insulin is crucial for diabetes management.
• Understanding the factors influencing insulin absorption is key to optimizing glycemic control.

Purpose of the Study:

• To investigate the relationship between subcutaneous blood flow (SBF) and the absorption rate of short-acting insulin in diabetic patients.
• To elucidate the mechanisms governing insulin transport in subcutaneous tissue.

Main Methods:

• Simultaneous measurement of 125I-labelled insulin disappearance and 133Xe washout (to assess SBF) in 23 diabetic patients.
• Induction of SBF alterations using orthostatic changes, local heat, or cold.
• In vitro diffusion studies of insulin in agar gel at 37°C.

Main Results:

• Insulin absorption rate demonstrated a curvilinear relationship with SBF.
• A near-linear correlation was observed at SBF levels below 2-3 ml/(min·100 g).
• At higher SBFs, insulin absorption increased less proportionally, suggesting saturation or diffusion limitations.

Conclusions:

• Short-acting insulin absorption is significantly influenced by SBF in a non-linear manner.
• The findings suggest a diffusion-limited transport mechanism in the interstitial space.
• Increased blood flow may enhance insulin absorption by recruiting capillaries, increasing surface area, and reducing diffusion distances.