In vivo relationship between insulin and endothelin role of insulin-resistance

Since endothelin production is stimulated in vitro by insulin, we performed this study to evaluate in vivo the relationships between endothelin and insulin plasma levels during a glucose load. We studied 28 subjects; 17 with normal glucose tolerance (NGT) and 11 with impaired glucose tolerance (IGT). Ten of the subjects in this study were normotensive and 18 with mild to moderate hypertension. Age, sex and body mass index were comparable among the groups. After a 2-week period of washout they underwent an oral glucose tolerance test; blood was drawn at 0 (basal), 90 and 120 min after the load for determination of glucose, insulin, C-peptide of insulin and endothelin-1 and -2. Basal endothelin in all the subjects under study was correlated with basal insulin; moreover it was negatively related with the glucose:insulin ratio that has been considered as an insulin-sensitivity index and positively with the insulin:C-peptide ratio as hepatic insulin-resistance index. The relationship between basal endothelin and insulin values was also found in each glucose tolerance group. At 120 min after the glucose load, mean plasma values of endothelin were significantly higher (6.66 +/- 1.31 vs 4.17 +/- 0.61 pmol/L); moreover, the per cent increase of endothelin at 120 min was positively related to the per cent increase of insulin. Between the normotensive and hypertensive groups there were no significant differences in studied endothelin parameters. Our results appear to confirm that, even in vivo, insulin modulates circulating endothelin levels.