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|12||Tumour necrosis factor-alpha infusion produced insulin resistance but no change in the incretin effect in healthy volunteers.|
Nielsen ST; Lehrskov-Schmidt L; Krogh-Madsen R; Solomon TP; Lehrskov-Schmidt L; Holst JJ; Moller K
Diabetes Metab Res Rev 2013; 29(8): 655-63
PubMed ID: 23904405
BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumour necrosis factor-alpha (TNF-alpha). Although TNF-alpha infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce peripheral insulin resistance, the influence of this cytokine on the incretin effect is unknown. METHODS: We investigated whether systemic inflammation induced by TNF-alpha infusion in healthy volunteers alters the incretin hormone response to oral and intravenous glucose loads in a crossover study design with ten healthy male volunteers (mean age 24 years, mean body mass index 23.7 kg/m(2) ). The study consisted of four study days: days 1 and 2, 6-h infusion of saline; days 3 and 4, 6-h infusion of TNF-alpha; days 1 and 3, 4-h oral glucose tolerance test; and days 2 and 4, 4-h corresponding intravenous isoglycaemic glucose tolerance test. Glucose tolerance tests were initiated after 2 h of saline/TNF-alpha infusion. Plasma concentrations of TNF-alpha, interleukin 6, glucose, incretin hormones, and cortisol, and serum concentrations of C-peptide and insulin were measured throughout the study days. Insulin sensitivity was estimated by the Matsuda index and homeostasis model assessment of insulin resistance (HOMA-IR). Prehepatic insulin secretion rates were calculated. RESULTS: TNF-alpha infusion induced symptoms of systemic inflammation; increased plasma levels of cortisol, TNF-alpha, and interleukin 6; and increased the HOMA-IR. The secretion of incretin hormones as well as the incretin effect remained unchanged. CONCLUSION: In healthy young male volunteers, acute systemic inflammation induced by infusion of TNF-alpha is associated with insulin resistance with no change in the incretin effect. Copyright (c) 2013 John Wiley & Sons, Ltd. Nielsen, Signe Tellerup