Enhanced glucose utilization during prolonged glucose clamp studies.

Abstract

Glucose clamp studies were performed to see if glucose utilization increased during extended periods of moderate hyperinsulinemia (80–100 μu/ml). Modifications of the standard euglycemic clamp were performed, and the amount of glucose metabolized (M) and the metabolic clearance rate (MCR) of glucose were calculated for each 10-min interval during the study. In seven subjects, the clamp was performed for 180 min, with the glucose infusion rate fixed from 120 to 180 min at the rate necessary to maintain basal plasma glucose concentration from 80 to 120 min. Under these conditions, mean plasma glucose concentration fell 18% during the last 60 min of the study, indicating increased glucose utilization. Twenty-four subjects, nonobese and obese normals and type II diabetics, had 3-h clamp studies performed. We documented an average increase of M by 21% and MCR by 28% in the third hour as compared with the second hour. Five-hour clamp studies in nine subjects and 8-h studies in two subjects indicated a continued rise in glucose MCR, until a plateau was reached at 4–6 h after initiation of hyperinsulinemia (mean = 88 μU/ml). This plateau was approximately 85% above the MCR of the last 30 min of a standard glucose clamp. Measurement of glucose turnover with 3H-3-glucose suggested that increasing suppression of hepatic glucose production was not responsible for the increases in glucose utilization noted. Insulin binding to erythrocytes was determined in 13 subjects before and after 180 min of hyperinsulinemia, and showed decreased total specific insulin binding. In a two-component high- and low-affinity model of insulin binding, the observed decrease in total insulin binding was primarily caused by a decrease in the high-affinity receptor component. These results suggested that glucose utilization continuously increased during a 5-h period of constant hyperinsulinemia, and this was due possibly to enhanced insulin sensitivity. This change took place in spite of a concomitant decrease in number of insulin receptors.