The adipocyte IKK/NFkappaB pathway: A therapeutic target for insulin resistance

Hong Ruan, Henry J. Pownall

Research output: Contribution to journalReview article

19 Scopus citations

Abstract

Insulin suppresses the release of non-esterified fatty acids from adipocytes and suppresses glucose production from hepatocytes, but stimulates glucose uptake by skeletal muscle, liver and adipose tissue. Insulin resistance, the failure of an ample supply of insulin to mediate these effects, is an early and fundamental defect in type 2 diabetes (T2D) associated with obesity. Adipose tissue not only acts as an energy depot, but also secretes a variety of endocrine, paracrine and autocrine factors, which regulate energy metabolism and insulin activity. In addition, adipose tissue from obese individuals has a distinct secretory profile that alters both adipocyte function and overall in vivo insulin sensitivity. Obesity is coupled to insulin resistance and diabetes through the action of adipose-derived factors, in a process that involves intricate signaling pathways and transcriptional regulators in various cell types of adipose tissue, in addition to cross-talk between adipose and non-adipose tissues. Thus, the dissection of the specific pathways that contribute to insulin resistance in obese individuals is a crucial component in understanding obesity-linked T2D. In this review, recent in vitro and in vivo data that implicate the IKK (inhibitor of κappaB kinase)/NFκappaB pathway, a component of both fatty acid and inflammatory cytokine signaling cascades, in the regulation of insulin sensitivity are discussed, and the value of this pathway as a therapeutic target in T2D is evaluated.

Original languageEnglish (US)
Pages (from-to)346-352
Number of pages7
JournalCurrent Opinion in Investigational Drugs
Volume10
Issue number4
StatePublished - Apr 1 2009

Keywords

  • Adipose tissue
  • Diabetes
  • Energy metabolism
  • Fatty acid
  • Glucose
  • IKK
  • Inflammatory cytokine
  • Inhibitor of ?B kinase
  • Insulin resistance
  • Macrophage
  • NF?B
  • Obesity

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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