INSULIN ACTION AND HEPATIC GLUCOSE CYCLING IN CUSHINGS-SYNDROME

Citation
Ap. Heaney et al., INSULIN ACTION AND HEPATIC GLUCOSE CYCLING IN CUSHINGS-SYNDROME, Clinical endocrinology, 46(6), 1997, pp. 735-743
Citations number
37
Categorie Soggetti
Endocrynology & Metabolism
Journal title
ISSN journal
03000664
Volume
46
Issue
6
Year of publication
1997
Pages
735 - 743
Database
ISI
SICI code
0300-0664(1997)46:6<735:IAAHGC>2.0.ZU;2-N
Abstract
OBJECTIVE Although it is well established hypercortisolism causes insu lin resistance, mechanisms responsible for impaired insulin action in Gushing's syndrome are unclear, This study investigated the contributi on of the glucose/glucose-6-phosphate substrate cycle (G/G6P). PATIENT S Eight patients with Gushing's syndrome and seven control subjects we re studied, All had normal fasting plasma glucose, DESIGN Insulin acti on was assessed using the euglycaemic glucose clamp at insulin infusio n rates of 0.4 and 2.0 mU/kg/min combined with a simultaneous infusion of [2(3)H]- and [6(3)-H]-glucose, Glucose/glucose-6-phosphate cycle a ctivity was calculated as the difference in glucose turnover rates det ermined separately for [2(3)H]- and [6(3)H]-glucose by selective enzym atic detritiation. MEASUREMENTS AND RESULTS Exogenous glucose infusion rates required to maintain euglycaemia were significantly lower in Gu shing's patients compared to controls, during the 0.4 mU/kg/min (7.8 /- 1.2 vs 15.7 +/- 0.5 mu mol/kg/min, P<0.001) and the 2.0 mU/kg/min i nsulin infusions (26.2 +/- 2.8 vs 51.5 +/- 3.5 mu mol/kg/min, P<0.001) . Endogenous glucose production was similar in both groups in the post absorptive state (10.2 +/- 0.3 vs 10.8 +/- 0.4 mu mol/kg/min, P = 0.50 ) and suppressed to a similar degree during hyperinsulinaemia. G/G6P c ycle activity was markedly increased in the Gushing's group in the pos tabsorptive state (5.4 +/- 1.1 vs 2.0 +/- 0.5 mu mol/kg/min, P = 0.028 ) and during the 0.4 mU/kg/min (3.2 +/- 0 6 vs 1.2 +/- 0.4 mu mol/kg/m in, P = 0.014) and 2.0 mU/kg/min insulin infusions (3.3 +/- 0.8 vs 1.1 +/- 0.5 mu mol/kg/min, P = 0.049), CONCLUSIONS Patients with Gushing' s syndrome show marked peripheral insulin resistance and enhanced hepa tic G/G6P cycle activity, In the fasting state increased glucose/gluco se-6-phosphate cycle activity may be a protective mechanism limiting h yperglycaemia, During hyperinsulinaemia G/G6P cycle activity was incre ased but insulin resistance was predominantly due to reduced periphera l glucose uptake.