A rodent model of rapid-onset diabetes induced by glucocorticoids and high-fat feeding.

Journal Article (Journal Article)

Glucocorticoids (GCs) are potent pharmacological agents used to treat a number of immune conditions. GCs are also naturally occurring steroid hormones (e.g. cortisol, corticosterone) produced in response to stressful conditions that are thought to increase the preference for calorie dense 'comfort' foods. If chronically elevated, GCs can contribute to the development of type 2 diabetes mellitus (T2DM), although the mechanisms for the diabetogenic effects are not entirely clear. The present study proposes a new rodent model to investigate the combined metabolic effects of elevated GCs and high-fat feeding on ectopic fat deposition and diabetes development. Male Sprague-Dawley rats (aged 7-8 weeks) received exogenous corticosterone or wax (placebo) pellets, implanted subcutaneously, and were fed either a standard chow diet (SD) or a 60% high-fat diet (HFD) for 16 days. Animals given corticosterone and a HFD (cort-HFD) had lower body weight and smaller relative glycolytic muscle mass, but increased relative epididymal mass, compared with controls (placebo-SD). Cort-HFD rats exhibited severe hepatic steatosis and increased muscle lipid deposition compared with placebo-SD animals. Moreover, cort-HFD animals were found to exhibit severe fasting hyperglycemia (60% increase), hyperinsulinemia (80% increase), insulin resistance (60% increase) and impaired β-cell response to oral glucose load (20% decrease) compared with placebo-SD animals. Thus, a metabolic syndrome or T2DM phenotype can be rapidly induced in young Sprague-Dawley rats by using exogenous GCs if a HFD is consumed. This finding might be valuable in examining the physiological and molecular mechanisms of GC-induced metabolic disease.

Full Text

Duke Authors

Cited Authors

  • Shpilberg, Y; Beaudry, JL; D'Souza, A; Campbell, JE; Peckett, A; Riddell, MC

Published Date

  • September 2012

Published In

Volume / Issue

  • 5 / 5

Start / End Page

  • 671 - 680

PubMed ID

  • 22184636

Pubmed Central ID

  • PMC3424464

Electronic International Standard Serial Number (EISSN)

  • 1754-8411

Digital Object Identifier (DOI)

  • 10.1242/dmm.008912


  • eng

Conference Location

  • England