Effect of subcutaneous glucose sensor implantation on skin mRNA expression in pigs.
BACKGROUND
Tight glycemic control has the potential to reduce long- and short-term effects of diabetes mellitus. New and improved glucose sensors for short-term implantation in the subcutis offer an alternative to the classical self-monitored blood glucose concentration in the management of diabetes. The use of glucose sensors has an advantage over the latter due to its capacity to obtain continuous glucose measurements. However, instability of in vivo glucose sensor measurements has been reported, and this bioinstability is likely to be influenced by the inflammatory reaction to the implanted sensor. Gene expression analysis is now performed in an existing porcine model of subcutaneous glucose sensor implantation to investigate the time course of inflammation from a new perspective.


METHODS
Tissue surrounding glucose sensors was sampled to different time points (2 h, 24 h, 3 days, and 7 days) after implantation in the subcutis of pigs. From the tissue RNA was extracted, cDNA was synthesized, and real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed for the quantification of immunoregulatory genes.


RESULTS
Genes coding for adhesion molecules, chemokines, cytokines, CD markers, and antigen presentation molecules were differentially expressed over time. Most of the investigated genes were significantly up-regulated 24 h and 7 days after implantation.


CONCLUSIONS
The present study demonstrated that the technology for targeted multiple-gene expression by real-time RT-PCR is useful in the evaluation of the immune response to subcutaneously implanted glucose sensors and that the expression levels also seemed to correspond to the histomorphological observations over time.
Kvist
Peter Helding
PH
Biopharmaceuticals Research Unit, Department of Histology, Novo Nordisk A/S, Måløv, Denmark. PHKv@novonordisk.com
Iburg
Tine
T
Dawson
Harry Dale
HD
Jensen
Henrik Elvang
HE
D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D004567:Electrodes, Implanted / Q000009:adverse effects*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007249:Inflammation / Q000378:metabolism*; D008422:Materials Testing; D018670:Monitoring, Ambulatory / Q000295:instrumentation*; D020556:Neutrophil Infiltration; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D040521:Subcutaneous Tissue / Q000378:metabolism* / Q000473:pathology; D034421:Sus scrofa; D013997:Time Factors; D015854:Up-Regulation
D001786:Blood Glucose; D012333:RNA, Messenger