{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T21:12:06Z","timestamp":1776114726839,"version":"3.50.1"},"reference-count":50,"publisher":"American Diabetes Association","issue":"12","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":2844,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:p>Tumor necrosis factor-\u03b1 (TNF-\u03b1) has widespread metabolic actions. Systemic TNF-\u03b1 administration, however, generates a complex hormonal and metabolic response. Our study was designed to test whether regional, placebo-controlled TNF-\u03b1 infusion directly affects insulin resistance and protein breakdown. We studied eight healthy volunteers once with bilateral femoral vein and artery catheters during a 3-h basal period and a 3-h hyperinsulinemic-euglycemic clamp. One artery was perfused with saline and one with TNF-\u03b1. During the clamp, TNF-\u03b1 perfusion increased glucose arteriovenous differences (0.91 \u00b1 0.17 vs. 0.74 \u00b1 0.15 mmol\/L, P = 0.012) and leg glucose uptake rates. Net phenylalanine release was increased by TNF-\u03b1 perfusion with concomitant increases in appearance and disappearance rates. Free fatty acid kinetics was not affected by TNF-\u03b1, whereas interleukin-6 (IL-6) release increased. Insulin and protein signaling in muscle biopsies was not affected by TNF-\u03b1. TNF-\u03b1 directly increased net muscle protein loss, which may contribute to cachexia and general protein loss during severe illness. The finding of increased insulin sensitivity, which could relate to IL-6, is of major clinical interest and may concurrently act to provide adequate tissue fuel supply and contribute to the occurrence of systemic hypoglycemia. This distinct metabolic feature places TNF-\u03b1 among the rare insulin mimetics of human origin.<\/jats:p>","DOI":"10.2337\/db13-0138","type":"journal-article","created":{"date-parts":[[2013,7,9]],"date-time":"2013-07-09T03:40:07Z","timestamp":1373341207000},"page":"4023-4029","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":44,"title":["Direct Effects of TNF-\u03b1 on Local Fuel Metabolism and Cytokine Levels in the Placebo-Controlled, Bilaterally Infused Human Leg"],"prefix":"10.2337","volume":"62","author":[{"given":"Ermina","family":"Bach","sequence":"first","affiliation":[{"name":"Medical Research Laboratories, Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark"},{"name":"Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Infectious Diseases, Aarhus University Hospital, Aarhus, 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