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No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients.
Paquot, Nicolas; Castillo, M. J.; Lefebvre, Pierre et al.
2000In Journal of Clinical Endocrinology and Metabolism, 85 (3), p. 1316-9
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Keywords :
Adult; Blood Glucose/metabolism; Female; Humans; Hyperinsulinism/blood; Immunoglobulin Heavy Chains/analysis/pharmacology; Immunoglobulin gamma-Chains; Injections, Intravenous; Insulin/blood/physiology; Insulin Resistance/physiology; Male; Middle Aged; Obesity/physiopathology; Receptors, Tumor Necrosis Factor/analysis/physiology; Recombinant Fusion Proteins/analysis/pharmacology; Recombinant Proteins/pharmacology; Single-Blind Method; Tumor Necrosis Factor-alpha/pharmacology
Abstract :
[en] Inhibition of tumor necrosis factor (TNF)-alpha results in a marked increase in insulin sensitivity in obese rodents. We investigated the influence of a TNF antagonist [Ro 45-2081, a recombinant fusion protein that consists of the soluble TNF-receptor (p55) linked to the Fc portion of human IgG1] on insulin sensitivity of patients with android obesity. Seven patients (five women and two men; mean +/- SD age, 41 +/- 4 yr; body mass index, 36.1 +/- 4.7 kg/m2; waist to hip ratio, 0.99 +/- 0.11) were studied (three patients with normal glucose tolerance and four patients with impaired glucose tolerance or mild diabetes; all were hyperinsulinemic). Each patient underwent two consecutive euglycemic hyperinsulinemic glucose-clamp tests: 48 h after injection of placebo and 48 h after a single i.v. injection of 50 mg Ro 45-2081. In both tests, steady-state plasma glucose and insulin levels were similar. Insulin-mediated glucose disposal (2.23 +/- 0.74 vs. 2.38 +/- 0.99 mg/kg(-1) x min(-1)) and glucose metabolic clearance rate (2.28 +/- 0.85 vs. 2.48 +/- 1.03 mL/kg(-1) x min(-1)) were similar after placebo and after the drug. Indirect calorimetry showed no difference in substrate oxidation rates between the two experimental conditions. In conclusion, under the conditions of this study, no improvement in insulin sensitivity was observed in obese insulin-resistant patients following a single i.v. administration of a recombinant TNF receptor: Fc fusion protein.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Paquot, Nicolas ;  Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques
Castillo, M. J.
Lefebvre, Pierre ;  Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques
Scheen, André  ;  Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques - Médecine interne générale
Language :
English
Title :
No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients.
Publication date :
2000
Journal title :
Journal of Clinical Endocrinology and Metabolism
ISSN :
0021-972X
eISSN :
1945-7197
Publisher :
Endocrine Society, Chevy Chase, United States - Maryland
Volume :
85
Issue :
3
Pages :
1316-9
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 06 May 2009

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