Cystic fibrosis (CF) patients are insulin-resistant with regards to suppression of hepatic glucose production and proteolysis, but the effect of insulin on adipose free fatty acid (FFA) release has not been studied. [9,10-3H]palmitate kinetics were measured in 11 stable adult CF patients with impaired glucose tolerance (IGT) and 9 normal control subjects. Baseline plasma palmitate concentrations [CF = 99 ± 13 (median 74, range 65 to 187); control = 88 ± 9 (88, 46 to 138) μmol/L, P = .9] and palmitate flux [CF = 114 ± 11 (100, 72 to 171); control = 105 ± 12 (106, 54 to 182) μmol/min, P = 0.9] were not different between CF patients and controls. During a euglycemic clamp with infusion of insulin to physiologic postprandial levels, however, palmitate concentrations tended to be higher in CF patients: CF = 18 ± 3 (13, 10 to 47), control = 12 ± 1 (11, 8 to 18) μmol/L, P = 0.08. The higher palmitate concentrations during hyperinsulinemia appeared to be due to reduced suppression of adipose tissue palmitate release, because mean palmitate flux was 33% greater in CF subjects [32 ± 5 (26, 17 to 66) μmol/min] than controls: [24 ± 2 (23, 17 to 34) μmol/min], P = .20. There was considerably greater heterogeneity in insulin-induced suppression of plasma palmitate concentration and flux in CF patients compared to normal control subjects. In summary, a defect in insulin suppression of lipolysis was seen in clinically stable CF patients with IGT, similar to what has been described in CF for amino acid and glucose metabolism. This quantitative difference in lipolysis may account for inadequate insulin-induced suppression of hepatic glucose production in CF, and may be a metabolic adaptation to increased energy needs.
Bibliographical noteFunding Information:
Supported by a grant from the Cystic Fibrosis Foundation and Grants No. DK45343, DK50456 (Minnesota Obesity Center), and NIH-M01-RR-00400 (General Clinical Research Center) from the US Public Health Service.
Copyright 2008 Elsevier B.V., All rights reserved.