Basal glucose homeostasis with and without fixed concentrations of glucagon and insulin

Abstract

The aim of this study was to investigate the extent to which the basal steady state could be maintained with fixed concentrations of glucagon and insulin. To this end, arterial plasma glucose concentrations and peripheral glucose uptake (using the forearm technique) were compared in healthy men (age 19 to 23 years) in the normal postabsorptive state and after suppression of endogenous pancreatic secretion. Two groups (A and B), each consisting of four men, were studied. In group A, the study comprised a control period (I) of 40 minutes followed by a test period (II) of 180 minutes during which normal pancreatic secretion was maintained throughout. In group B, the study comprised a control period (I) of 40 minutes, a stabilization period (II) of 120 minutes, and a test period (III) of 120 minutes. After the control period with normal pancreatic secretion, a new steady state with fixed hormone concentrations was established during the first 90 minutes of period II using simultaneous infusions of somatostatin (250 μg/h), insulin (0.15 mU/kg/min) and glucagon, the latter being adjusted to maintain a stable arterial glucose level similar to the preceding control concentration. Thereafter, without further adjustement of the glucagon infusion rate, observations were continued during period III to assess the maintenance of the steady state. In group A, the range of variation in arterial glucose concentrations during periods I and II was 4.0 ± 0.9 and 6.5 ± 1.3 mg/dL, respectively. In group B, the variation in glucose levels (mg/dL) was similar in period I (3.3 ± 0.9) and the final 30 minutes of period II (3.0 ± 0.4), but was increased to 20.4 ± 5.4 in period III. During the latter, mean glucose concentrations rose from 97 ± 3 to 109 ± 5 mg/dL after 45 minutes and then declined to 92 ± 6 mg/dL ( P < .02) by 120 minutes while forearm glucose uptake (FGU: .050 ± .015 mg 100 mL forearm/min ) remained unchanged. The conclusions drawn from this study are as follows: (1) Fixed basal levels of glucagon and insulin, in contrast to normal islet secretion, may result in markedly unstable glucose concentrations; (2) because the latter were not associated with any change in FGU, this instability was probably the result of changes in hepatic glucose output (HGO) rather than peripheral glucose uptake; (3) The technique of islet secretory blockade with fixed basal insulin and glucagon concentrations should be used with caution for investigating the control of HGO in man unless the influence to the technique alone is initially defined.