The Acute Effects of Low-Dose TNF-α on Glucose Metabolism and β-Cell Function in Humans

Abstract EN

Type 2 diabetes is characterized by increased insulin resistance and impaired insulin secretion.

Type 2 diabetes is also associated with low-grade inflammation and increased levels of proinflammatory cytokines such as TNF-α.

TNF-α has been shown to impair peripheral insulin signaling in vitro and in vivo.

However, it is unclear whether TNF-α may also affect endogenous glucose production (EGP) during fasting and glucose-stimulated insulin secretion (GSIS) in vivo.

We hypothesized that low-dose TNF-α would increase EGP and attenuate GSIS.

Recombinant human TNF-α or placebo was infused in healthy, nondiabetic young men ( n = 10 ) during a 4-hour basal period followed by an intravenous glucose tolerance test (IVGTT).

TNF-α lowered insulin levels by 12% during the basal period ( P < 0.05 ).

In response to the IVGTT, insulin levels increased markedly in both trials, but there was no difference between trials.

Compared to placebo, TNF-α did not affect EGP during the basal period.

Our results indicate that TNF-α acutely lowers basal plasma insulin levels but does not impair GSIS.

The mechanisms behind this are unknown but we suggest that it may be due to TNF-α increasing clearance of insulin from plasma without impairing beta-cell function or hepatic insulin sensitivity.