Abstract
Insulin has metabolic and vascular effects in the human body. What mechanisms that orchestrate the effects in the microcirculation, and how the responds differ in different tissues, is however not fully understood. It is therefore of interest to search for markers in microdialysate that may be related to the microcirculation. This study aims to identify proteins related to microvascular changes in different tissue compartments after glucose provocation using in vivo microdialysis. Microdialysis was conducted in three different tissue compartments (intracutaneous, subcutaneous and intravenous) from healthy subjects. Microdialysate was collected during three time periods; recovery after catheter insertion, baseline and glucose provocation, and analyzed using proteomics. Altogether, 126 proteins were detected. Multivariate data analysis showed that the differences in protein expression levels during the three time periods, including comparison before and after glucose provocation, were most pronounced in the intracutaneous and subcutaneous compartments. Four proteins with vascular effects were identified (angiotensinogen, kininogen-1, alpha-2-HS-glycoprotein and hemoglobin subunit beta), all upregulated after glucose provocation compared to baseline in all three compartments. Glucose provocation is known to cause insulin-induced vasodilation through the nitric oxide pathway, and this study indicates that this is facilitated through the interactions of the RAS (angiotensinogen) and kallikrein-kinin (kininogen-1) systems.
Highlights
Insulin has metabolic and vascular effects in the human body
In order to understand what mechanisms that orchestrate the effects in the microcirculation, investigation of the microdialysate in the search for other markers important for the microcirculation during a glucose provocation is of interest
By examining the protein expression in microdialysis samples, this study aims to identify protein biomarkers that are related to microvascular changes in different tissue compartments during an oral glucose provocation
Summary
Insulin has metabolic and vascular effects in the human body. What mechanisms that orchestrate the effects in the microcirculation, and how the responds differ in different tissues, is not fully understood. This study aims to identify proteins related to microvascular changes in different tissue compartments after glucose provocation using in vivo microdialysis. The metabolic and vascular effects of insulin in the human skin have previously been investigated using microdialysis technique[8,9]. It is known that oral glucose provocation, and thereby endogenously increased insulin, increases local tissue blood flow in the human skin. This is partially to increase access to glucose, through a process primarily believed to be mediated by endothelial insulin dependent vasodilation. It is known that glucose provocation has microcirculatory effects, partly dependent on the vascular effects of insulin, but the effects on changes in local protein expression are lacking. In order to understand what mechanisms that orchestrate the effects in the microcirculation, investigation of the microdialysate in the search for other markers important for the microcirculation during a glucose provocation is of interest
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