Distinct but nonadditive effects of epinephrine and cortisol on determinants of glucose tolerance in dogs

Abstract

Effects of physiological increments of epinephrine (Epi) and cortisol (F) on glucose metabolism were assessed in dogs just before and during an intravenous glucose tolerance test performed in the last 3 h of an acute (short F + Epi, 4 h F and 3.5 h Epi) or prolonged (long F + Epi, 75 h F and Epi) infusion period. Comparison of the F + Epi effects with those of F and Epi alone enabled us to describe interactions between these hormones. The increase in plasma glucose after long F + Epi [from control (saline, Sal) of 5.2 +/- 0.1 to 5.8 +/- 0.1 mmol/l; n = 8; P less than 0.01] was not greater than the sum of the glucose increments after long F and long Epi individually. Long Epi and long F both reduced glucose tolerance (KGlc) significantly, but the decline during long F + Epi (from Sal 3.6 +/- 0.7 to 2.9 +/- 0.5%/min; P greater than 0.1) was less than during either individual infusion. Minimal model analysis showed that F attenuated the inhibitory effects of long Epi on glucose-mediated glucose disposal (SGlc), so that it was not reduced from 3.8 +/- 0.8 (Sal) during long F + Epi compared with the fall to 1.3 +/- 0.7 x 10(-2) min-1 (n = 6; P less than 0.05) during long Epi alone. F had the dominant influence on insulin sensitivity (SI) during infusion of F + Epi. The reduction of SI from 8.4 +/- 1.1 (Sal) to 6.6 +/- 1.2 (short F + Epi) and 5.1 +/- 1.1 x 10(-4) min-1 per mU/l (long F + Epi; P less than 0.05) paralleled that seen with F alone but contrasted with the acute reduction of SI during short Epi (4.8 +/- 1.5; P less than 0.02 vs. Sal) and its restoration to control values of 9.0 +/- 2.1 x 10(-4) min-1 per mU/l during long Epi. We conclude that Epi and F have distinct but nonadditive effects on determinants of glucose tolerance.

Insulin secretion, insulin sensitivity and glucose‐mediated glucose disposal in Cushing's disease: a minimal model analysis

“…One other important observation of the present study was the distinct elevation of basal insulin and C-peptide levels and insulin secretory responses to the glucose load in the untreated Cushing's disease patients. This hyperinsulinaemia has been noted in other studies (Perley & Kipnis, 1966;Martin et al, 1991;Beard et al, 1984) and may reflect the insulin-resistant state (Martin et al, 1991), or represent a direct response of the p cells of the islets to high circulating cortisol levels (Kern & Logothetopoulos, 1970). Given the fact that basal C-peptide levels were also elevated and that the insulin clearance parameter (P,) was similar in Cushing's disease and control subjects, it probably reflects a true hypersecretion of insulin in these subjects.…”

“…However, such studies do not distinguish between insulin-mediated (SI) and glucose-mediated (SG) glucose disposal, both of which contribute to overall glucose tolerance of an individual (Bergman et al, 1985). The impact of glucocorticoid excess on SI and SG has been reported in only one study in dogs after 72 hours of exposure to hydrocortisone infusion, where SI decreased significantly but SG was unchanged (Martin et al, 1991). In the present study median SG was reduced by 40% in the Cushing's disease subjects with long-standing glucocorticoid excess but was not statistically significant.…”

“…In addition, the numerous experimental techniques and the variable glucose and insulin levels at which test procedures are performed make studies difficult to interpret (Rizza el al., 1982;Stojanovska et al, 1990;McMahon et al, 1988). For instance, apart from one study in dogs (Martin et al, 1991), the majority of these studies failed to quantitate glucosemediated glucose disposal, which is the ability of hypergly-Clinical Endocrinology (1991) 35 caemia to enhance glucose removal independent of insulin (Bergman et al, 1985;Bergman, 1989;Kahn et al, 1990) and which is an important determinant of glucose tolerance (Bergman er al., 1985;Bergman, 1989). Kahn and coworkers (1 990) have recently shown that glucose-mediated glucose disposal is differently regulated from insulinmediated glucose disposal in the presence of acute and longterm insulinopenia.…”

Glucose Effectiveness in Two Subtypes Within Impaired Glucose Tolerance: A Minimal Model Analysis

“…and reduced S G (6). Short-term infusion of norepinephrine (36) and epinephrine (37,38) and prolonged infusion of growth hormone and cortisol (37) reduced Sj but did not affect S G . On the other hand, prolonged infusion of epinephrine (38) and hyperglycemia caused by insulin deficiency induced by somatostatin reduced S G but not S r (22).…”