Author/Editor		Carey, AL; Steinberg, GR; Macaulay, SL; Thomas, WG; Holmes, AG; Ramm, G; Prelovšek, O; Hohnen-Behrens, C; Watt, MJ; James, DE
Title		Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase
Type		članek
Source		Diabetes
Vol. and No.		Letnik 55, št. 10
Publication year		2006
Volume		str. 2688-97
Language		eng
Abstract		Although interleukin-6 (IL-6) has been associated with insulin resistance, little is known regarding the effects of IL-6 on insulin sensitivity in humans in vivo. Here, we show that IL-6 infusion increases glucose disposal without affecting the complete suppression of endogenous glucose production during a hyperinsulinemic-euglycemic clamp in healthy humans. Because skeletal muscle accounts for most of the insulin-stimulated glucose disposal in vivo, we examined the mechanism(s) by which IL-6 may affect muscle metabolism using L6 myotubes. IL-6 treatment increased fatty acid oxidation, basal and insulin-stimulated glucose uptake, and translocation of GLUT4 to the plasma membrane. Furthermore, IL-6 rapidly and markedly increased AMP-activated protein kinase (AMPK). To determine whether the activation of AMPK mediated cellular metabolic events, we conducted experiments using L6 myotubes infected with dominant-negative AMPK alpha-subunit. The effects described above were abrogated in AMPK dominant-negative-infected cells. Our results demonstrate that acute IL-6 treatment enhances insulin-stimulated glucose disposal in humans in vivo, while the effects of IL-6 on glucose and fatty acid metabolism in vitro appear to be mediated by AMPK.
Descriptors		ADULT AMINOIMIDAZOLE CARBOXAMIDE ANIMALS CELL LINE CELL MEMBRANE FATTY ACIDS GLUCOSE GLUCOSE CLAMP TECHNIQUE HYPERINSULINISM INSULIN INTERLEUKIN-6 MICE MICE, KNOCKOUT MULTIENZYME COMPLEXES PROTEIN-SERINE-THREONINE KINASES RATS RECOMBINANT PROTEINS RIBONUCLEOTIDES SIGNAL TRANSDUCTION