IS THE TISSUE AVAILABILITY OF CIRCULATING INSULIN-LIKE-GROWTH-FACTOR-I INVOLVED IN ORGAN DAMAGE AND GLUCOSE REGULATION IN HYPERTENSION

Background Besides its capacity to regulate organ and tissue growth, t he insulin-like growth factor I exerts biologic actions that resemble those of insulin. Tissue access of the factor depends on the distribut ion of the circulating bound factor between its binding protein 3 that remains within the intravascular space and its binding protein 1 that is able to cross the endothelium. Objective To investigate whether th e distribution of the circulating factor between its binding proteins is altered in patients with essential hypertension and whether this is related to changes in organ damage and glucose regulation in these pa tients, Design The study subjects were 30 never-treated patients with essential hypertension and 27 age-and sex-matched normotensive control s, Methods Serum insulin-like growth factor I-binding proteins 3 and 1 and plasma insulin-like growth factor I levels were determined by spe cific radioimmunoassays, Results Insulin-like growth factor I levels w ere significantly higher in the hypertensive patients than they were i n the normotensive controls, Whereas the serum level of binding protei n 1 was significantly higher in hypertensives than it was in controls, we found no differences in the level of binding protein 3 between the two groups. With the upper 100% confidence limit of the normotensive population as the cut-off point, a subgroup of 16 hypertensives had an abnormally high serum level of binding protein 1. Compared with patie nts with normal binding protein 1 levels, patients with increased bind ing protein 1 levels were characterized by the following: lower fastin g glucose and insulin levels, lower insulin: glucose ratios, lower tri glyceride levels, higher left ventricular mass indexes, higher creatin ine clearances and higher urinary albumin excretion rates, The serum b inding protein 1 level was correlated inversely to the plasma insulin level for the whole group of hypertensives. Conclusions These results show that the distribution of circulating insulin-like growth factor I between its binding proteins 1 and 3 is altered in essential hyperten sion, Thus, there is a subgroup (53%) of hypertensive patients with in creased serum levels of insulin-like growth factor I-binding protein 1 . Access of the circulating factor to tissues is more easily achieved in these patients, The clinical characteristics of this subgroup of pa tients suggest that the tissue availability of insulin-like growth fac tor I is a determinant of organ damage and insulin sensitivity in esse ntial hypertension.