The acute effects of low-dose TNF-α on glucose metabolism and β-cell function in humans.
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| Abstract |
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.
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| Authors | Tobias Ibfelt, Christian P Fischer, Peter Plomgaard, Gerrit van Hall, Bente Klarlund Pedersen |
| Journal | Mediators of inflammation (Mediators Inflamm) Vol. 2014 Pg. 295478 ( 2014) ISSN: 1466-1861 [Electronic] United States |
| PMID | 24692847 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't) |
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