Age-related analysis of glucose metabolism in spontaneously hypertensive and normotensive rats.

This study was designed to investigate the effect of both hypertension and ageing on the efficiency of glucose metabolism. A 12-sample, 120 min intravenous glucose tolerance test (IVGTT) was applied to 36 rats: two groups of nine young (12 weeks) spontaneously hypertensive and Wistar Kyoto rats (Y-SHR and Y-WKY group, respectively) and two groups of nine old (40 weeks) SHR and WKY rats (O-SHR and O-WKY group, respectively). Insulinaemia and glycaemia data were interpreted in terms of estimates of glucose effectiveness, S(G), and insulin sensitivity, S(I), provided by the minimal model of glucose kinetics. The possible link between insulin resistance and hypertension was investigated by comparing Y-SHR vs. Y-WKY and O-SHR vs. O-WKY groups. Comparison of O-SHR vs. Y-SHR and O-WKY vs. Y-WKY groups enabled us to investigate the role of age in the development of abnormalities in glucose metabolism. No significant differences (P > 0.05) were observed in the mean S(G) and S(I) estimates between SHR and age-matched WKY groups. This finding indicates that exposure of SHR to high blood pressure levels does not necessarily lead to the development of insulin resistance and impaired glucose effectiveness. Similarly, no significant differences (P > 0.05) were observed in S(G) and S(I) estimates between old and young SHR and WKY groups. This finding indicates that, in this animal model of hypertension, insulin sensitivity and glucose effectiveness do not even deteriorate with ageing.

Interaction between glucose metabolism and endogenous insulin release in hypertension.

The minimal model approach was applied to examine the dynamic interaction between glucose metabolism and endogenous insulin release during an intravenous glucose tolerance test (IVGTT) in a group of hypertensive patients (H group) compared with a group of normotensive subjects (N group). A modified version of the classical minimal model of C-peptide kinetics and secretion was used to evaluate the total amount of insulin secretion per unit of distribution volume (TIS) together with 3 indexes of beta-cell function (the basal, Phi(b), first, Phi1, and second phase, Phi2, beta-cell sensitivity to glucose). These indexes were associated with estimates of glucose effectiveness (S(G)) and insulin sensitivity (S(I)) provided by the classical minimal model of glucose kinetics. No significant differences were found in Phi(b), Phi1, and Phi2 estimates between the H group and the N group. In the H group, the average TIS was 54% higher (P <.05) than in the N group, while S(G) and S(I) estimates showed a 44% decrease (P <.05) and a 51% decrease (P <.05), respectively. These results suggest that hyperglycemia observed in our H group during IVGTT is a compensatory response to insulin resistance (low S(I)) and to the reduced ability of glucose to promote its own metabolism (low S(G)). This hyperglycemic state causes a larger than normal stimulation of beta cell, which explains insulin hypersecretion (higher TIS) even in the presence of normal beta-cell sensitivity values of Phi(b), Phi1, and Phi2.