Is the tissue availability of circulating insulin-like growth factor I involved in organ damage and glucose regulation in hypertension?

Abstract

BACKGROUND: Besides its capacity to regulate organ and tissue growth, the insulin-like growth factor I exerts biologic actions that resemble those of insulin. Tissue access of the factor depends on the distribution 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 the 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 patients.

DESIGN: The study subjects were 30 never-treated patients with essential hypertension and 27 age- and sex-matched normotensive controls.

METHODS: Serum insulin-like growth factor I-binding proteins 3 and 1 and plasma insulin-like growth factor I levels were determined by specific radioimmunoassays.

RESULTS: Insulin-like growth factor I levels were significantly higher in the hypertensive patients than they were in the normotensive controls. Whereas the serum level of binding protein 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 patients with normal binding protein 1 levels, patients with increased binding protein 1 levels were characterized by the following: lower fasting glucose and insulin levels, lower insulin: glucose ratios, lower triglyceride levels, higher left ventricular mass indexes, higher creatinine clearances and higher urinary albumin excretion rates. The serum binding 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 hypertension. Thus, there is a subgroup (53%) of hypertensive patients with increased 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 patients suggest that the tissue availability of insulin-like growth factor I is a determinant of organ damage and insulin sensitivity in essential hypertension.