Enzymatic glycocalyx treatment impairs insulin‐mediated recruitment of microvascular blood volume and decreases insulin sensitivity in rats

Abstract

Agonist‐induced impairment of the blood‐exclusion properties of the glycocalyx has been shown to effectively increase microvascular blood volume (MBV) (VanTeeffelen, CVR 2010). Since the rapid insulin‐mediated increase in MBV has been suggested to contribute to insulin's metabolic actions (Vincent, Diabetes 2004), we hypothesize that loss of glycocalyx impairs the ability of insulin to increase MBV and to subsequently dispose blood glucose.In rats, loss of glycocalyx was induced by a bolus of hyaluronidase; saline served as control. During anesthesia the microcirculation of hindlimb muscle was visualized with a Side Stream Dark field camera before and during intravenous insulin infusion. The RBC column width distribution of visible microvessels was determined in time. In control, median RBC column width did not change during insulin infusion but the P75 and P90 increased rapidly (<10 min) with 0.3 ± 0.1 μm and 0.8 ± 0.4 μm respectively. In the hyaluronidase treated group insulin had no effect on median, P75 and P90 of RBC column width. To measure insulin sensitivity an intravenous insulin tolerance test was performed in conscious rats. The insulin‐mediated decline in blood glucose after 15 minutes was found to be decreased after hyaluronidase treatment from 62 ± 1 to 53 ± 2% (P<0.05).It is concluded that glycocalyx degradation is associated with an impaired ability for insulin to increase MBV and to dispose glucose.Supported by DFN 2006.00.027 and NHF 2005T037