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Diabetes Metab Res Rev. 2013 Nov;29(8):655-63. doi: 10.1002/dmrr.2441.

Tumour necrosis factor-alpha infusion produced insulin resistance but no change in the incretin effect in healthy volunteers.

Author information

1
Centre of Inflammation and Metabolism and CMRC, Section 7641 Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

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-α). Although TNF-α 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-α 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-α; 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-α infusion. Plasma concentrations of TNF-α, 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-α infusion induced symptoms of systemic inflammation; increased plasma levels of cortisol, TNF-α, 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-α is associated with insulin resistance with no change in the incretin effect.

KEYWORDS:

glucose; incretins; insulin resistance; systemic inflammation; tumour necrosis factor-alpha

PMID:
23904405
DOI:
10.1002/dmrr.2441
[Indexed for MEDLINE]

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