Cited by 1,961Adipokines, Inflammation, and Metabolic DiseasesAdvanced Glycation End Products researchDiabetes Management and Research

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Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans: Role of Oxidative Stress

Esposito, Katherine, Nappo, Francesco, Marfella, Raffaele, Giugliano, Giovanni, Giugliano, Francesco, Ciotola, Myriam, Quagliaro, Lisa, Ceriello, Antonio, Giugliano, Dario·2002·Circulation

DOI 10.1161/01.cir.0000034509.14906.ae

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Abstract

Background— Circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are elevated in diabetic patients. We assessed the role of glucose in the regulation of circulating levels of IL-6, TNF-α, and interleukin-18 (IL-18) in subjects with normal or impaired glucose tolerance (IGT), as well as the effect of the antioxidant glutathione. Methods and Results— Plasma glucose levels were acutely raised in 20 control and 15 IGT subjects and maintained at 15 mmol/L for 5 hours while endogenous insulin secretion was blocked with octreotide. In control subjects, plasma IL-6, TNF-α, and IL-18 levels rose ( P <0.01) within 2 hours of the clamp and returned to basal values at 3 hours. In another study, the same subjects received 3 consecutive pulses of intravenous glucose (0.33 g/kg) separated by a 2-hour interval. Plasma cytokine levels obtained at 3, 4, and 5 hours were higher ( P <0.05) than the corresponding values obtained during the clamp. The IGT subjects had fasting plasma IL-6 and TNF-α levels higher ( P <0.05) than those of control subjects. The increase in plasma cytokine levels during the clamping lasted longer (4 hours versus 2 hours, P <0.01) in the IGT subjects than in the control subjects, and the cytokine peaks of IGT subjects after the first glucose pulse were higher ( P <0.05) than those of control subjects. On another occasion, 10 control and 8 IGT subjects received the same glucose pulses as above during an infusion of glutathione; plasma cytokine levels did not show any significant change from baseline after the 3 glucose pulses. Conclusions— Hyperglycemia acutely increases circulating cytokine concentrations by an oxidative mechanism, and this effect is more pronounced in subjects with IGT. This suggests a causal role for hyperglycemia in the immune activation of diabetes.

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Authors: Esposito, K., Nappo, F., Marfella, R., Giugliano, G., Giugliano, F., Ciotola, M., Quagliaro, L., Ceriello, A., & Giugliano, D.
Affiliations: University of Udine (IT)
ORCID: Esposito, Katherine
Marfella, Raffaele
Ceriello, Antonio
Giugliano, Dario
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2002-10-15
Volume: 106
Issue: 16
Pages: 2067-2072
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/01.cir.0000034509.14906.ae
OpenAlex: W2123560318
Cited by: 1,961
References: 36
Citations by year: 2026: 57 · 2025: 69 · 2024: 88 · 2023: 95 · 2022: 106 · 2021: 91 · 2020: 102 · 2019: 83 · 2018: 86 · 2017: 70 · 2016: 87 · 2015: 112 · 2014: 99 · 2013: 102 · 2012: 101
FWCI: 38.18
Type: journal article
Language: en
Open access: closed
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Institutional Research Information System (University of Udine) (submittedVersion)
Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords: hyperglycemia, inflammatory cytokines, interleukin-6, TNF-α, IL-18, impaired glucose tolerance, glutathione, oxidative stress, glucose clamp
MeSH terms: Adult, Antioxidants, Blood Glucose, Diabetes Mellitus, Type 2, Female, Glucose Tolerance Test, Glutathione, Humans, Inflammation, Kinetics, Male, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines, Glucose Intolerance, Oxidative Stress, Interleukin-18

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Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans: Role of Oxidative Stress

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