Microcirculatory dysfunctions Present in Early Stages of Metabolic Alterations in a Diabetic Mouse Model in vivo

Abstract

Vascular alterations are the most common causes of morbidity and mortality in diabetic patients. Despite the impact of endothelial dysfunction on microcirculatory properties, little is known about the endothelial cell alteration during the development of diabetes. For that reason we monitored continuously in vivo functional and morphological alterations of the micorvasculature in normoglycaemic, hyperinsulinemic and hyperlpidaemic transgenic UCP1/DTA-mice with brown fat deficiency, using a dorsal skin-fold chamber preparation and fluorescence microscopy. Our results demonstrate functional as well as morphological microvascular alterations in 12 week old UCP1/DTA mice characterized by normoglycaemic values with an impaired glucose-tolerance. Similar, but more advanced alterations have been found in elder UCP1/DTA mice with early stage diabetes. In opposite to 20 week old UCP1/DTA mice, at this early stage of metabolic dysfunction there were no alterations found in parameters such as BFR and LEI. Permeability is already at this stage increased, as well as vessel density, vessel diameter and vessel distribution. In summary these results underline the necessity to recognize and control hyperglycaemic peaks and hyperlipidaemia early, even before there is a clinical status of diabetes mellitus. The microvascular alterations found in the experiments with acute hyperglycaemia, hyperinsulinimia and hyperlipidaemia in control mice, support the role of metabolic parameters in endothelial dysfunction.