The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Tumor necrosis factor impairs insulin action on peripheral glucose disposal and hepatic glucose output.
Abstract
The present study examined whether a prolonged infusion of tumor necrosis factor (TNF) into rats could sustain the increased rate of whole body glucose metabolism observed with short term exposure, and whether TNF produced hepatic or peripheral insulin resistance. Basal glucose metabolism was determined with the use of [3-3H]glucose 18 h after initiating a constant infusion of recombinant human TNF (1 microgram/kg.h). Thereafter, a two-step euglycemic hyperinsulinemic clamp was performed to determine whether TNF impaired insulin action. The overnight infusion of TNF minimally elevated plasma glucose concentrations (17%), but produced large increases in the whole body rate of glucose production and utilization (133%). Under hyperinsulinemic conditions, the glucose infusion rate necessary to maintain euglycemia was 30% lower in TNF-treated rats, indicating an insulin-resistant condition. This resulted from an impaired ability of insulin to both suppress hepatic glucose production and stimulate peripheral glucose utilization in TNF-infused animals. A second series of experiments was performed, using the in vivo tracer [U-14C]2-deoxyglucose technique, to elucidate which tissues were responsible for the TNF-induced increase in basal (no exogenous insulin) glucose disposal and peripheral insulin resistance. Under basal conditions, TNF increased glucose uptake by various muscles (gastrocnemius, heart, and diaphragm) as well as nonmuscle tissues (liver, lung, spleen, gut, skin and fat). Because of their relatively large mass and/or high rate of glucose uptake, the increased uptake by skin (25%), intestine (24%), muscle (23%), and liver (15%) accounted for the majority of the TNF-induced increment in whole body glucose disposal. Under euglycemic hyperinsulinemic conditions, the increment in glucose uptake by muscle and skin (85%) accounted for the majority of the glucose disposal in control rats. However, in TNF-infused animals, hyperinsulinemia failed to increase glucose uptake by skin and blunted the insulin-mediated increase in muscle by 73%. These results suggest that sustained elevations of TNF during chronic therapy and prolonged production of TNF by patients and experimental animals with malignancies or infectious diseases may be an important mechanism for the enhanced glucose flux as well as the insulin resistance seen in these conditions.
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In the citing paper
“In contrast to such distributions, there are reports that IL-6 and TNF-a seem to be equally synthesised by the different sites (28,36,53 -59) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [28]
In the citing paper
“Thus, leptin is preferentially expressed and secreted by subcutaneous adipose tissue (52) , while the expression of adiponectin, visfatin, omentin, resistin, PAI-1, IL-8, IL-7, IL-1a, MCP-1, TGF-b, growth-related oncogena, CCL5 and MIP-1b is higher in abdominal fat.”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [28]
In the citing paper
“In addition, the profile of adipokines produced is dissimilar between the subcutaneous and abdominal adipose tissues.”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [28]
Citations
Cites
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Mészáros, K., Lang, C. H., Bagby, G. J., & Spitzer, J. J. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)60912-3 · Cited by 153
Self-citationEffect of endotoxin-induced monokines on glucose metabolism in the muscle cell line L6.
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Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518
Hotamisligil, G. S., Peraldi, P., Budavari, A., Ellis, R., White, M. F., & Spiegelman, B. M. (1996) · Science · doi:10.1126/science.271.5249.665 · Cited by 2,630
Elective induction versus spontaneous labor after sonographic diagnosis of fetal macrosomia.
Combs, C. A., Singh, N. B., & Khoury, J. C. (1993) · PubMed · Cited by 2,463
Inflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066
Yuan, M., Konstantopoulos, N., Lee, J., Hansen, L., Li, Z.-W., Karin, M., & Shoelson, S. E. (2001) · Science · doi:10.1126/science.1061620 · Cited by 1,884
Metadata
- Authors
- Lang, C. H., Dobrescu, C., & Bagby, G. J.
- Affiliations
- Louisiana State University (US)
- ORCID
- Lang, C H
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1992-01
- Volume
- 130
- Issue
- 1
- Pages
- 43-52
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2067057146
- Cited by
- 535
- References
- 31
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 2 · 2022: 9 · 2021: 10 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 13 · 2016: 15 · 2015: 11 · 2014: 18 · 2013: 24 · 2012: 17
- FWCI
- 9.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01gm032654-10)
- National Institute of General Medical Sciences (GM 32654, GM 38032)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- TNF-α, insulin resistance, hepatic glucose production, hyperinsulinemic-euglycemic clamp, glucose uptake, muscle glucose uptake, whole-body glucose metabolism
- MeSH terms
- Animals, Glucose, Insulin Antagonists, Insulin Resistance, Liver, Male, Rats, Inbred Strains, Tumor Necrosis Factor-alpha, Rats
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