Tissue availability of insulin-like growth factor I is inversely related to insulin resistance in essential hypertension: effects of angiotensin converting enzyme inhibition.
BACKGROUND
The insulin-like growth factor I possesses 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 I that is able to cross the endothelium. Preliminary results have shown that tissue availability of insulin-like growth factor I is a determinant of glucose regulation in essential hypertension


OBJECTIVE
To investigate whether the tissue availability of circulating insulin-like growth factor I in patients with essential hypertension is related to insulin resistance and whether chronic angiotensin converting enzyme inhibition influences tissue availability of the factor and insulin resistance in these patients.


METHODS
We studied 29 patients with essential hypertension and 20 age-matched and sex-matched normotensive subjects. The measurements were repeated for 25 patients after 12 months of treatment with lisinopril. Tissue availability of circulating insulin-like growth factor I was assessed by analyzing its distribution between its binding proteins 3 and 1. An insulin resistance index was estimated using the homeostasis model analysis of fasting insulin-glucose interactions. Levels of serum insulin-like growth factor I binding proteins 3 and 1, plasma insulin-like growth factor I, and insulin were determined by specific radioimmunoassays.


RESULTS
Baseline insulin resistance index was significantly higher in the hypertensive patients than it was in the normotensive controls. With the upper 100% confidence limit of the normotensive population as the cutoff point, a subgroup of 12 hypertensives had an abnormally high insulin resistance index. Compared with patients with normal insulin resistance indexes, patients with greater than normal indexes were characterized by lower binding protein 1 levels, similar binding protein 3 levels, lower binding protein 1 : binding protein 3 ratio and similar insulin-like growth factor I levels. The serum binding protein 1 level and the binding protein 1 : binding protein 3 ratio were inversely correlated to the insulin resistance index for the whole group of hypertensives. After treatment with lisinopril hypertensive patients with higher than normal insulin resistance indexes at baseline exhibited normalization of this parameter and significant increases of binding protein 1 levels and binding protein 1 : binding protein 3 ratio, with no significant changes in insulin-like growth factor I levels. These parameters remained unchanged for the remaining patients.


CONCLUSIONS
These results suggest that tissue availability of circulating insulin-like growth factor I is a determinant of insulin sensitivity in patients with essential hypertension. Whereas the patients with normal insulin sensitivity exhibit greater than normal tissue access of circulating insulin-like growth factor I, patients with insulin resistance present normal tissue access of the factor. Our findings suggest that the ability of angiotensin converting enzyme inhibitors to restore insulin sensitivity in essential hypertensives may be related to their ability to facilitate the tissue availability of circulating insulin-like growth factor I.
Laviades
C
C
Division of Nephrology, San Jorge General Hospital, Huesca, Spain.
Gil
M J
MJ
Monreal
I
I
González
A
A
Díez
J
J
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005934:Glucagon / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood / Q000187:drug effects; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism*; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005934:Glucagon; D017706:Lisinopril