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Dose-Dependent Effects of Recombinant Human Interleukin-6 on Glucose Regulation
Abstract
Inflammatory cytokines have metabolic actions that probably contribute to the general adaptation of the organism during infectious or inflammatory stress. To examine the effects of interleukin 6 (IL-6), the main circulating cytokine, on glucose metabolism in man, we performed dose-response studies of recombinant human IL-6 in normal volunteers. Increasing single doses of IL-6 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/Kg BW) were injected sc in 15 healthy male volunteers (3 in each dose) after a 12-h fast. All IL-6 doses were tolerated well and produced no significant adverse effects. We measured the circulating levels of glucose, insulin, C-peptide, and glucagon at baseline and half-hourly over 4 h after the IL-6 injection. Mean peak plasma levels of IL-6 were achieved between 120 and 240 min and were 8, 22, 65, 290, and 4050 pg/mL, respectively, for the 5 doses. After administration of the 2 smaller IL-6 doses, we observed no significant changes in plasma glucose levels, which, because of continued fasting, decreased slightly over time. By 60 min after the 3 higher IL-6 doses, however, the decline in fasting blood glucose was arrested, and glucose levels increased in a dose-dependent fashion. The concurrent levels of plasma insulin and C-peptide were not affected by any IL-6 dose. In contrast, IL-6 caused significant increases in plasma glucagon levels, which peaked between 120 and 150 min after the IL-6 injection. In conclusion, sc IL-6 administration induced dose-dependent increases in fasting blood glucose, probably by stimulating glucagon release and other counteregulatory hormones and/or by inducing peripheral resistance to insulin action.
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“and causes hepatic and muscle insulin resistance in humans and in mice (39,55-60).”
From Expression of Mfn2, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [60]
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Metadata
- Authors
- Tsigos, C., Papanicolaou, D. A., Kyrou, I., Defensor, R., Mitsiadis, C. S., & Chrousos, G. P.
- Affiliations
- National Institutes of Health (US)
- Hellenic National Center for Research, Prevention and Treatment of Diabetes Mellitus and its Complications (C.T., I.K.), Athens 106 75, Greece
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1997-12-01
- Volume
- 82
- Issue
- 12
- Pages
- 4167-4170
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2086682722
- Cited by
- 324
- References
- 23
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 17 · 2017: 10 · 2016: 11 · 2015: 8 · 2014: 21 · 2013: 9 · 2012: 16
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- interleukin-6, glucose regulation, glucagon, insulin, C-peptide, dose-response relationship, inflammatory cytokines, insulin resistance, fasting blood glucose
- MeSH terms
- Adult, Blood Glucose, C-Peptide, Dose-Response Relationship, Drug, Glucagon, Humans, Injections, Subcutaneous, Insulin, Male, Recombinant Proteins, Interleukin-6
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