Glucose is the component of diabetic plasma that increases vascular permeability

Abstract

Diabetes mellitus is characterised by hyperglycaemia and an increased vascular permeability, which contribute to the development of cardiovascular complications. The underlying pathogenic mechanisms involved in the progression of diabetic microangiopathy are poorly understood, as most methods used to determine permeability with respect to diabetes do not control for compounding haemodynamic factors. Using the Landis-Michel technique (Michel, 1974) we investigated the effect of diabetic plasma on hydraulic conductivity (Lp) and reflection coefficient (σ) in mesenteric microvessels of R.temporaria in vivo. Perfusion of single microvessels with dialysed (10kDa) diabetic plasma had no effect on Lp (4.2 ± 0.74 and 3.9 ± 0.58 [mean ± sem x 10−7cm.s−1.cmH2O−1], for 5% human serum albumin (HSA) and diabetic plasma, respectively, p>0.05, n=8) or σ (0.75 ± 0.045 and 0.67 ± 0.035 [mean ± sem], for 5% HSA and diabetic plasma, respectively; p>0.05, n=8). Addition of exogenous glucose (final concentration 20mM) to plasma however, caused a significant, sustained increase in Lp (2.0 ± 1.13 and 7.66 ± 3.20, for 5% HSA and diabetic plasma with 20mM glucose, respectively, p<0.01, n=7). No significant change in σ was observed (0.77 ± 0.02 and 0.76 ± 0.09 [mean ± sem], for 5% HSA and diabetic plasma with 20mM glucose, respectively; p>0.05, n=8). The increase in macromolecular solute flux seen in diabetic patients may therefore be directly attributable to glucose dependent increased convective flux of macromolecules due to increased hydraulic conductivity. Supported by the BHF.