Human aging is associated with altered TNF-α production during hyperglycemia and hyperinsulinemia

John P. Kirwan, Raj K. Krishnan, James A. Weaver, Luis F. Del Aguila, William J. Evans

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84 Scopus citations


Changes in tumor necrosis factor-α (TNF-α) may provide a mechanism to explain impaired glucose metabolism with advancing age. Hyperglycemic clamps (180 min, 10 mM) were performed on seven older [67 ± 2 yr; body mass index (BMI) 24.7 ± 1.0 kg/m2] and seven younger (22 ± 1 yr; BMI 21.8 ± 1.3 kg/m2) healthy sedentary males with normal glucose tolerance. TNF-α production at basal and at the end of 180 min of hyperglycemia and hyperinsulinemia was measured ex vivo from lipopolysaccharide-stimulated (1 ng/ml) peripheral blood mononuclear cells. Plasma glucose, insulin, and C-peptide levels were similar in both groups at basal and during the last 30 min of the hyperglycemic clamp. Glucose infusion rates were lower (P < 0.004) in the older group compared with the young, indicating decreased insulin action among the older subjects. Basal TNF-α secretion was similar in older and younger subjects. TNF-a was suppressed (P < 0.02) in the younger group (230 ± 46 vs. 126 ± 49 pg/ml; basal vs. clamp) but not in the older group (153 ± 37 vs. 182 ± 42 pg/ml), with significant group differences in response (P < 0.05). A significant correlation was observed between the level of suppression in TNF-α production and insulin action (Kendall's rank, τ = 0.40, P < 0.05). Furthermore, the TNF-α response during the clamp was related to fat mass (r = 0.88, P < 0.001) and abdominal fat (r = 0.81, P < 0.003). In conclusion, these findings suggest a possible mechanism by which TNF-α may modulate glucose metabolism in younger people. Aging and modest increases in adiposity prevent the "normal" suppression of TNF-α production after a sustained postprandial-like hyperglycemic-hyperinsulinemic stimulus, which may contribute in part to the decline in insulin sensitivity in older men.

Original languageEnglish (US)
Pages (from-to)E1137-E1143
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number6 44-6
StatePublished - 2001
Externally publishedYes


  • Abdominal adiposity
  • Diabetes
  • Insulin resistance
  • Obesity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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