Effect of adipocyte β 3-adrenergic receptor activation on the type 2 diabetic MKR mice

Hyunsook Kim, Patricia A. Pennisi, Oksana Gavrilova, Stephanie Pack, William Jou, Jennifer Setser-Portas, Joyce East-Palmer, Yan Tang, Vincent C. Manganiello, Derek LeRoith

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

The antiobesity and antidiabetic effects of the β 3- adrenergic agonists were investigated on nonobese type 2 diabetic MKR mice after injection with a β 3-adrenergic agonist, CL-316243. An intact response to acute CL-316243 treatment was observed in MKR mice. Chronic intraperitoneal CL-316243 treatment of MKR mice reduced blood glucose and serum insulin levels. Hyperinsulinemic euglycemic clamps exhibited improvement of the whole body insulin sensitivity and glucose homeostasis concurrently with enhanced insulin action in liver and adipose tissue. Treating MKR mice with CL-316243 significantly lowered serum and hepatic lipid levels, in part due to increased whole body triglyceride clearance and fatty acid oxidation in adipocytes. A significant reduction in total body fat content and epididymal fat weight was observed along with enhanced metabolic rate in both wild-type and MKR mice after treatment. These data demonstrate that β 3- adrenergic activation improves the diabetic state of nonobese diabetic MKR mice by potentiation of free fatty acid oxidation by adipose tissue, suggesting a potential therapeutic role for β 3-adrenergic agonists in nonobese diabetic subjects.

Original languageEnglish (US)
Pages (from-to)E1227-E1236
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume290
Issue number6
DOIs
StatePublished - 2006

Keywords

  • Insulin-like growth factor I receptor mutation
  • Type 2 diabetes

ASJC Scopus subject areas

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

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