title: The effect of cortisol on glucose/glucose-6-phosphate cycle activity and insulin action.
abstract: Increased glucose/glucose-6-phosphate (G/G6P) substrate cycle activity may be an early marker of disordered hepatic glucose metabolism. To investigate the effects of glucocorticoids on G/G6P cycle activity and insulin resistance, we studied eight normal subjects using the euglycemic glucose clamp technique with high pressure liquid chromatography-purified [2(3)H]- and [6-3H]glucose tracers at insulin infusion rates of 0.4 and 2.0 mU/kg.min after 24-h cortisol (2 micrograms/kg.min) and saline infusions. Endogenous glucose production ([6-3H]glucose) was greater after cortisol than saline in the postabsorptive state (13.3 +/- 0.5 vs. 12.2 +/- 0.5 mumol/kg.min; P < 0.05) and during 0.4-mU insulin infusion (10.5 +/- 0.7 vs. 5.0 +/- 0.8 mumol/kg.min; P < 0.005). During 2.0-mU insulin infusion, endogenous glucose production was suppressed similarly (5.1 +/- 0.4 vs. 4.1 +/- 0.5 mumol/kg.min), but glucose disappearance was less after cortisol than saline (38.7 +/- 3.5 vs. 64.6 +/- 4.3 mumol/kg.min; P < 0.001). G/G6P cycle activity after cortisol and saline was similar in the postabsorptive state and during 0.4 mU insulin. During 2.0 mU insulin, cycle activity was greater after cortisol than saline (3.6 +/- 0.9 vs. 0.8 +/- 0.5 mumol/kg.min; P < 0.005). In conclusion, cortisol induces hepatic insulin resistance without significantly changing G/G6P cycle activity. At high glucose turnover rates, G/G6P cycle activity is increased by cortisol; however, reduced glucose disappearance is the main cause of impaired insulin action.
authors.affiliation: Sir George E. Clark Metabolic Unit, B.S. Royal Victoria Hospital, Belfast, Northern Ireland.
authors.forename: D P
authors.initials: DP
authors.lastname: Rooney
authors.forename: R D
authors.initials: RD
authors.lastname: Neely
authors.forename: C
authors.initials: C
authors.lastname: Cullen
authors.forename: C N
authors.initials: CN
authors.lastname: Ennis
authors.forename: B
authors.initials: B
authors.lastname: Sheridan
authors.forename: A B
authors.initials: AB
authors.lastname: Atkinson
authors.forename: E R
authors.initials: ER
authors.lastname: Trimble
authors.forename: P M
authors.initials: PM
authors.lastname: Bell
mesh_terms: D000042:Absorption; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male
chemical_list: D001786:Blood Glucose; D005958:Glucosephosphates; D007328:Insulin; D019298:Glucose-6-Phosphate; D005947:Glucose; D006854:Hydrocortisone