Abstract:
:It has recently been observed in situ in mice that insulin takes approximately 10 min to be transported 20 microm into the t-tubule networks of skeletal muscle fibers. The mechanisms for this slow transport are unknown. It has been suggested that the biochemical composition of the t-tubular space that may include large molecules acting as gels and increased viscosity in the narrow tubules may explain this slow diffusion. In this article, we construct a mathematical model of insulin transport within the t-tubule network to determine potential mechanisms responsible for this slow insulin transport process. Our model includes insulin diffusion, insulin binding to insulin receptors, t-tubule network tortuosity, interstitial fluid viscosity, hydrodynamic wall effects, and insulin receptor internalization and recycling. The model predicted that depending on fiber type there is a 2-15 min delay in the arrival time of insulin between the sarcolemma and inner t-tubules (located 20 microm from the sarcolemma) after insulin injection. This is consistent with the experimental data. Increased viscosity in the narrow t-tubules and large molecules acting as gels are not the primary mechanisms responsible for the slow insulin diffusion. The primary mechanisms responsible for the slow insulin transport are insulin binding to insulin receptors and network tortuosity.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Shorten PR,McMahon CD,Soboleva TKdoi
10.1529/biophysj.107.107888subject
Has Abstractpub_date
2007-11-01 00:00:00pages
3001-7issue
9eissn
0006-3495issn
1542-0086pii
S0006-3495(07)71554-0journal_volume
93pub_type
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