title: The acute effects of low-dose TNF-α on glucose metabolism and β-cell function in humans.
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.
authors.affiliation: Department of Infectious Diseases and CMRC, The Centre of Inflammation and Metabolism (CIM), Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 7641 Blegdamsvej 9, 2100 Copenhagen, Denmark ; Copenhagen Muscle Research Centre, Rigshospitalet, 2100 Copenhagen, Denmark.
authors.forename: Tobias
authors.identifier: 0000-0003-4437-8892
authors.initials: T
authors.lastname: Ibfelt
authors.affiliation: Department of Infectious Diseases and CMRC, The Centre of Inflammation and Metabolism (CIM), Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 7641 Blegdamsvej 9, 2100 Copenhagen, Denmark ; Copenhagen Muscle Research Centre, Rigshospitalet, 2100 Copenhagen, Denmark.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Fischer
authors.affiliation: Department of Infectious Diseases and CMRC, The Centre of Inflammation and Metabolism (CIM), Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 7641 Blegdamsvej 9, 2100 Copenhagen, Denmark ; Copenhagen Muscle Research Centre, Rigshospitalet, 2100 Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Plomgaard
authors.affiliation: Department of Infectious Diseases and CMRC, The Centre of Inflammation and Metabolism (CIM), Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 7641 Blegdamsvej 9, 2100 Copenhagen, Denmark ; Copenhagen Muscle Research Centre, Rigshospitalet, 2100 Copenhagen, Denmark ; Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Gerrit
authors.initials: G
authors.lastname: van Hall
authors.affiliation: Department of Infectious Diseases and CMRC, The Centre of Inflammation and Metabolism (CIM), Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 7641 Blegdamsvej 9, 2100 Copenhagen, Denmark ; Copenhagen Muscle Research Centre, Rigshospitalet, 2100 Copenhagen, Denmark.
authors.forename: Bente Klarlund
authors.initials: BK
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D004311:Double-Blind Method; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose