Abstract

We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of the IκB kinase β (IKKβ) attenuated insulin signaling in cultured cells, whereas IKKβ inhibition reversed insulin resistance. Thus, IKKβ, rather than the cyclooxygenases, appears to be the relevant molecular target. Heterozygous deletion ( Ikkβ +/− ) protected against the development of insulin resistance during high-fat feeding and in obese Lep ob/ob mice. These findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus and identify the IKKβ pathway as a target for insulin sensitization.

Keywords

Insulin resistanceHyperinsulinemiaIκB kinaseEndocrinologyInternal medicineInsulinDyslipidemiaInsulin receptorObesityDiabetes mellitusType 2 Diabetes MellitusPathogenesisType 2 diabetesMedicineBiologyNF-κBInflammation

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Publication Info

Year
2001
Type
article
Volume
293
Issue
5535
Pages
1673-1677
Citations
1850
Access
Closed

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Cite This

Minsheng Yuan, Nicky Konstantopoulos, Jongsoon Lee et al. (2001). Reversal of Obesity- and Diet-Induced Insulin Resistance with Salicylates or Targeted Disruption of <i>Ikkβ</i>. Science , 293 (5535) , 1673-1677. https://doi.org/10.1126/science.1061620

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DOI
10.1126/science.1061620