The acute effects of low-dose TNF-α on glucose metabolism and β-cell function in humans

21 Citations (Scopus)


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.

Original languageEnglish
JournalMediators of Inflammation
Pages (from-to)295478
Publication statusPublished - 16 Feb 2014


  • Adult
  • Blood Glucose
  • Diabetes Mellitus, Type 2
  • Double-Blind Method
  • Glucose
  • Glucose Tolerance Test
  • Humans
  • Insulin
  • Insulin-Secreting Cells
  • Male
  • Recombinant Proteins
  • Signal Transduction
  • Tumor Necrosis Factor-alpha
  • Young Adult


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