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Inguinal Subcutaneous White Adipose Tissue (ISWAT) Transplantation Model of Murine Islets
Published on: February 16, 2020
Insulin depot formation in subcutaneoue tissue.
James P Leuenberger Jockel1, Philipp Roebrock, Oliver A Shergold
1Roche Diabetes Care AG, Burgdorf, Switzerland.
Journal of Diabetes Science and Technology
|February 27, 2013
Summary
Insulin depots from pumps spread laterally along the skin surface, not spherically as assumed. Depot formation depends on subcutaneous tissue structure and cell boundaries, following paths of least resistance.
Area of Science:
- Biomedical Engineering
- Pharmacokinetics
- Tissue Science
Background:
- Subcutaneous insulin delivery via pumps creates depots whose size and geometry are crucial for absorption.
- Conventional imaging methods lack the resolution and speed for accurate small-volume insulin depot visualization.
- Accurate visualization is needed to understand insulin pharmacokinetics and optimize delivery.
Purpose of the Study:
- To evaluate the size and geometry of insulin depots formed during subcutaneous insulin pump administration.
- To develop and apply a novel high-resolution method for visualizing small insulin depot volumes.
Main Methods:
- Developed a novel technique involving infusing dyed insulin into porcine tissue, followed by shock freezing.
- Utilized cryomicrotomy to slice frozen tissue and digital imaging to capture each layer.
- Employed proprietary software to reconstruct a 3D model of the insulin depot with high resolution (30x30 µm planar, 100 µm depth).
Main Results:
- Insulin depots do not form spheres as commonly assumed; they spread laterally parallel to the skin surface.
- Depot outreach increases with infused volume, reaching up to 7.1 mm for 50 µl.
- Significant lateral spread occurs within the collagen matrix binding adipose cells; perpendicular spread begins beyond ~100 µl.
Conclusions:
- Insulin depot formation is dictated by the opening of channels between adipose cells.
- Insulin follows the path of least resistance within the subcutaneous tissue.
- The local structure of subcutaneous tissue determines the final insulin depot geometry.
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