THE CONTRIBUTION OF INSULIN-DEPENDENT AND INSULIN-INDEPENDENT GLUCOSE-UPTAKE TO INTRAVENOUS GLUCOSE-TOLERANCE IN HEALTHY-HUMAN SUBJECTS

Glucose disposal occurs by both insulin-independent and insulin-depend ent mechanisms, the latter being determined by the interaction of insu lin sensitivity and insulin secretion. To determine the role of insuli n-independent and insulin-dependent factors in glucose tolerance, we p erformed intravenous glucose tolerance tests on 93 young healthy subje cts (55 male, 38 female; 18-44 years of age; body mass index, 19.5-52. 2 kg/m2). From these tests, we determined glucose tolerance as the glu cose disappearance constant (K(g)), calculated beta-cell function as t he incremental insulin response to glucose for 19 min after an intrave nous glucose bolus (IIR0-19), and derived an insulin sensitivity index (S(I)) and glucose effectiveness at basal insulin (S(G)) using the mi nimal model of glucose kinetics. To eliminate the effect of basal insu lin on S(G) and estimate insulin-independent glucose uptake, we calcul ated glucose effectiveness at zero insulin (GEZI = S(G) - [S(I) X basa l insulin]). Insulin-dependent glucose uptake was estimated as S(I) X IIR0-19, because the relationship between S, and beta-cell function ha s been shown to be hyperbolic. Using linear regression to determine th e influence of these factors on glucose tolerance, we found that GEZI was significantly related to K(g) (r = 0.70; P < 0.0001), suggesting a major contribution of insulin-independent glucose uptake to glucose d isappearance. As expected, S(I) X IIR0-19 also correlated well with K( g) (r = 0.74; P < 0.0001), confirming the importance of insulin-depend ent glucose uptake to glucose tolerance. Although IIR0-19 alone correl ated with K(g) (r = 0.35; P = 0.0005), S(I) did not (r = 0.18; P > 0.0 8). By multiple regression, 72% of the variance in K(g) could be expla ined by GEZI and S(I) x IIR0-19 (r = 0.85; P < 0.0001), We conclude th at insulin-independent glucose uptake is a major determinant of intrav enous glucose tolerance and that the interaction of insulin sensitivit y and insulin levels are more important than either factor alone as a determinant of intravenous glucose tolerance.