MKR mice are resistant to the metabolic actions of both insulin and adiponectin: Discordance between insulin resistance and adiponectin responsiveness

Chul Hee Kim, Patricia Pennisi, Hong Zhao, Shoshana Yakar, Jeanne B. Kaufman, Kenjiro Iganaki, Joseph Shiloach, Philipp E. Scherer, Michael J. Quon, Derek LeRoith

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Most rodent models of insulin resistance are accompanied by decreased circulating adiponectin levels. Adiponectin treatment improves the metabolic phenotype by increasing fatty acid oxidation in skeletal muscle and suppressing hepatic glucose production. Muscle IGF-I receptor (IGF-IR)-lysine-arginine (MKR) mice expressing dominant-negative mutant IGF-IRs in skeletal muscle are diabetic with insulin resistance in muscle, liver, and adipose tissue. Adiponectin levels are elevated in MKR mice, suggesting an unusual discordance between insulin resistance and adiponectin responsiveness. Therefore, we investigated the metabolic actions of adiponectin in MKR mice. MKR and ob/ob mice were treated both acutely (28 μg/g) and chronically (for 2 wk) with full-length adiponectin. Acute hypoglycemic effects of adiponectin were evident only in ob/ob mice but not in MKR mice. Chronic adiponectin treatment significantly improved both insulin sensitivity and glucose tolerance in ob/ob but not in MKR mice. Adiponectin receptor mRNA levels and adiponectin-stimulated phosphorylation of AMPK in skeletal muscle and liver were similar among MKR, wild-type, and ob/ob mice. Thus MKR mice are adiponectin resistant despite normal expression of adiponectin receptors and normal AMPK phosphorylation in muscle and liver. MKR mice may be a useful model for dissecting relationships between insulin resistance and adiponectin action in regulation of glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)E298-E305
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume291
Issue number2
DOIs
StatePublished - Jul 17 2006

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Keywords

  • Adiponectin resistance
  • Muscle insulin-like growth factor-I receptor-lysine-arginine mouse

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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