IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2011;3(4):257-265.

Original Article
Effect of cutaneous blood flow on absorption of insulin: A methodological study in
healthy male volunteers

Lydia A. Jakobsen, Anne Jensen, Lars E. Larsen, Morten R. Sørensen, Hans Christian Hoeck, Lars Arendt-Nielsen, Parisa Gazerani

Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Faculty of Medicine, Aalborg University,
Aalborg, Denmark; Center for Clinical and Basic Research (CCBR) and C4Pain, Aalborg, Denmark.

Received September 22, 2011; accepted October 19, 2011; Epub November 15, 2011; Published December 15, 2011

Abstract: Absorption of drugs from subcutaneous tissue depends on several factors, including tissue perfusion at the administration
site. Tissue perfusion can be manipulated by e.g. application of local heat. This may subsequently alter the rate or amount of
absorption of drugs from a subcutaneous depot. The aim of the present study was to investigate if increased tissue perfusion after
controlled local heating can change the absorption of subcutaneously administered high-concentration short-acting insulin (Actrapid®).
Thirteen healthy Caucasian males participated in two randomized experimental sessions; a session with locally applied controlled
heat at the injection site, and a control session without local heat application. Tissue perfusion (blood flow) was monitored with Laser
Doppler Imaging, and blood samples were taken to assess the levels of glucose and insulin. Local heat application at the site of
insulin injection significantly enhanced tissue perfusion by approximately 145%. However, no correlation was found between insulin
absorption and tissue perfusion. Based on our findings, it was concluded that tissue perfusion is not the rate-limiting factor in the
absorption of high-concentration short-acting insulin from a subcutaneous depot. Instead, dissociation of insulin hexamers into dimers
and monomers is suggested to constitute a greater barrier to absorption.  (IJPPP1109003).

Keywords: Local heat, skin perfusion, insulin, Actrapid®, subcutaneous depot, absorption

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Address all correspondence to:
Parisa Gazerani, Pharm D, PhD
Center for Sensory-Motor Interaction (SMI)
Department of Health Science & Technology
Aalborg University
Fredrik Bajers Vej 7-D3, DK-9220 Aalborg, Denmark
Phone +45 99 40 24 12
Fax +45 98 15 40 08
E-mail gazerani@hst.aau.dk