The Acute Effects of Low-Dose TNF-αon Glucose Metabolism andβ-Cell Function in Humans
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-αhas been shown to impair peripheral insulin signalingin vitroandin vivo. However, it is unclear whether TNF-αmay also affect endogenous glucose production (EGP) during fasting and glucose-stimulated insulin secretion (GSIS)in vivo. We hypothesized that low-dose TNF-αwould increase EGP and attenuate GSIS. Recombinant human TNF-αor 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-αlowered 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-αdid not affect EGP during the basal period. Our results indicate that TNF-αacutely 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-αincreasing clearance of insulin from plasma without impairing beta-cell function or hepatic insulin sensitivity.