Dynamics of Tolbutamide, Glucose, and Insulin Interrelationships Following Varying Doses of Intravenous Tolbutamide in Normal Subjects

Abstract

Four healthy adult subjects received intravenous tolbutamide (TOL) at six different doses (twenty-four tests): 0.0625 gin., 0.125 gin., 0.25 gm., 0.5 gin., 1.0 gm. and 1.5 gm. Blood glucose (BG), serum immunoreactive insulin (IRI) and serum TOL levels were determined before and for 180 minutes after TOL. There was a highly significant correlation of the dose of TOL with the peak IRI (p<.01), zero to ten minute IRI area (p<.001), and zero to sixty minute IRI area (p<.001) and with the decline in BG expressed as zero to sixty minute BG area (p<.001). Similar significant correlations were observed between levels of TOL and both IRI and BG. At each dose level the IRI response correlated significantly with the BG fall. An additional eighteen subjects received the 1.0 gm. dose. In these, serum TOL levels did not correlate with either BG or IRI. These subjects also received intravenous glucose (0.5 gm. per kilogram body weight). BG levels did not correlate with IRI. However, there were striking correlations between TOL and glucosestimulated peak IRI (p<.001), zero to ten minute IRI area (p<.001) and zero to sixty minute IRI area (p<.05). Also, the zero to ten minute BG areas in the two tests were negatively correlated (p<.05). The mean (± SEM) space of distribution for glucose (G.S.) and tolbutamide (T.S.) was found to be 13.45 ± 0.71 and 6.34 ± 0.31 L., respectively. There was a significant correlation between G.S. and T.S. (r = 0.70; p<.01). Within individuals a significant dose-response relationship exists between TOL and IRI. TOL- and glucose-induced IRI secretion dynamics suggest strong similarities between mechanisms of rapid IRI release and/or size of available IRI storage pools.