The Acute Effects of Low-Dose TNF-α on Glucose Metabolism and β-Cell Function in Humans. (16th February 2014)

• Record Type: Journal Article
• Authors: Ibfelt, Tobias; Fischer, Christian P.; Plomgaard, Peter; van Hall, Gerrit; Pedersen, Bente Klarlund
• Other Names: Reimund Jean-Marie Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2014(2014)
• Publication Date: 2014-02-16
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2014/295478
• Languages: English
• ISSNs: 0962-9351

Abstract

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.