Insulin transport within skeletal muscle transverse tubule networks

¹ AgResearch Limited

^* To whom correspondence should be addressed. E-mail: paul.shorten{at}agresearch.co.nz.

Submitted on March 4, 2007
Revised on April 18, 2007
Accepted on 25 June 2007

	Abstract

It has recently been observed in situ in mice that insulin takes approximately 10 minutes to be transported 20 µm into the t-tubule networks of skeletal muscle fibres. 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 paper 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 internalisation and recycling. The model predicted that depending on fibre type there is a 2-15 min delay in the arrival time of insulin between the sarcolemma and inner t-tubules (located 20 µm 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.

Key Words: Diffusion, Model, Receptor