Role of resistin in diet-induced hepatic insulin resistance

Evan D. Muse, Silvana Obici, Sanjay Bhanot, Brett P. Monia, Robert A. McKay, Michael W. Rajala, Philipp E. Scherer, Luciano Rossetti

Research output: Contribution to journalArticle

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Abstract

Resistin is an adipose-derived hormone postulated to link adiposity to insulin resistance. To determine whether resistin plays a causative role in the development of diet-induced insulin resistance, we lowered circulating resistin levels in mice by use of a specific antisense oligodeoxynucleotide (ASO) directed against resistin mRNA and assessed in vivo insulin action by the insulin-clamp technique. After 3 weeks on a high-fat (HF) diet, mice displayed severe insulin resistance associated with an approximately 80% increase in plasma resistin levels. in particular, the rate of endogenous glucose production (GP) increased more than twofold compared with that in mice fed a standard chow. Treatment with the resistin ASO for 1 week normalized the plasma resistin levels and completely reversed the hepatic insulin resistance. Importantly, in this group of mice, the acute infusion of purified recombinant mouse resistin, designed to acutely elevate the levels of circulating resistin up to those observed in the HF-fed mice, was sufficient to reconstitute hepatic insulin resistance. These results provide strong support for a physiological role of resistin in the development of hepatic insulin resistance in this model.

Original languageEnglish (US)
Pages (from-to)232-239
Number of pages8
JournalJournal of Clinical Investigation
Volume114
Issue number2
DOIs
StatePublished - Jul 2004

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Resistin
Insulin Resistance
Diet
Liver
Oligodeoxyribonucleotides
Insulin
Adiposity
High Fat Diet
Fats
Hormones
Glucose
Messenger RNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Muse, E. D., Obici, S., Bhanot, S., Monia, B. P., McKay, R. A., Rajala, M. W., ... Rossetti, L. (2004). Role of resistin in diet-induced hepatic insulin resistance. Journal of Clinical Investigation, 114(2), 232-239. https://doi.org/10.1172/JCI200421270

Role of resistin in diet-induced hepatic insulin resistance. / Muse, Evan D.; Obici, Silvana; Bhanot, Sanjay; Monia, Brett P.; McKay, Robert A.; Rajala, Michael W.; Scherer, Philipp E.; Rossetti, Luciano.

In: Journal of Clinical Investigation, Vol. 114, No. 2, 07.2004, p. 232-239.

Research output: Contribution to journalArticle

Muse, ED, Obici, S, Bhanot, S, Monia, BP, McKay, RA, Rajala, MW, Scherer, PE & Rossetti, L 2004, 'Role of resistin in diet-induced hepatic insulin resistance', Journal of Clinical Investigation, vol. 114, no. 2, pp. 232-239. https://doi.org/10.1172/JCI200421270
Muse ED, Obici S, Bhanot S, Monia BP, McKay RA, Rajala MW et al. Role of resistin in diet-induced hepatic insulin resistance. Journal of Clinical Investigation. 2004 Jul;114(2):232-239. https://doi.org/10.1172/JCI200421270
Muse, Evan D. ; Obici, Silvana ; Bhanot, Sanjay ; Monia, Brett P. ; McKay, Robert A. ; Rajala, Michael W. ; Scherer, Philipp E. ; Rossetti, Luciano. / Role of resistin in diet-induced hepatic insulin resistance. In: Journal of Clinical Investigation. 2004 ; Vol. 114, No. 2. pp. 232-239.
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