TY - JOUR

T1 - The Acute Effects of Low-Dose TNF-α on Glucose Metabolism and β-Cell Function in Humans

AU - Ibfelt, Tobias

AU - Fischer, Christian Philip

AU - Plomgaard, Peter

AU - van Hall, Gerrit

AU - Pedersen, Bente Klarlund

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Adult

KW - Blood Glucose

KW - Diabetes Mellitus, Type 2

KW - Double-Blind Method

KW - Glucose

KW - Glucose Tolerance Test

KW - Humans

KW - Insulin

KW - Insulin-Secreting Cells

KW - Male

KW - Recombinant Proteins

KW - Signal Transduction

KW - Tumor Necrosis Factor-alpha

KW - Young Adult

U2 - 10.1155/2014/295478

DO - 10.1155/2014/295478

M3 - Journal article

C2 - 24692847

VL - 2014

SP - 1

EP - 7

JO - Mediators of Inflammation

JF - Mediators of Inflammation

SN - 0962-9351

M1 - 295478

ER -