Recognizing that those with diabetes experience slow and incomplete wound healing because of a sluggish insulin metabolism, a team of researchers at the Max Planck Institute for Biology of Ageing, the Center for Molecular Medicine Cologne (CMMC), the CECAD Excellence Cluster, and the Institute of Genetics of the University of Cologne (all in Cologne, Germany) has gained new insights into the underlying cellular mechanisms. Their findings could lead to the development of new treatment methods.
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It had previously been assumed that high levels of glucose in the blood damages vessels and neurons and impairs the immune system, thereby accounting for wound healing problems. So the research group, led by Linda Partridge, director of the Max Planck Institute for Biology of Ageing, and Maria Leptin, professor at the Institute of Genetics of the University of Cologne, has now presented in a study that slowed insulin metabolism at the wound site directly affects neighboring cells involved in wound healing.
Parisa Kakanj, the author of the study, examined the skin of larvae of the fruit fly Drosophila melanogaster. These flies serve as models for diabetes because insulin metabolism has been strongly conserved over the course of evolution, meaning that flies and mammals are very similar in this respect. Using spinning-disk confocal microscopy (a type of fluorescence microscopy), Kakanj removed a cell from the outermost skin layer of fruit fly larvae using a precision laser and then observed what happens in the neighboring cells live under the microscope.
|(L-R) Time lapse of a wound healing in Drosophila: After removal of the nucleus (in yellow), the cell membrane (in pink) seals off the gap caused by the wound.|
"Immediately after a skin injury, the neighboring cells respond by forming an actomyosin cable," Kakanj explains. The cable consists of proteins that otherwise occur in muscle fibers, where they are responsible for muscular contraction. After an injury, the cable forms a contractile ring around the wound. It then contracts, sealing off the gap caused by the wound. "However, if insulin metabolism is impaired, as in our genetically modified flies, the cable is weaker and forms much later. This results in incomplete or slow wound healing," she adds.
New treatments for impaired wound healing could precisely target this mechanism. In the future, Kakanj explains, it may be possible to treat wound sites with drugs that locally activate insulin metabolism.
Full details of the work appear in the journal Nature Communications; for more information, please visit http://dx.doi.org/10.1038/ncomms12972.