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A rodent model of rapid-onset diabetes (ROD) induced by glucocorticoids and high-fat feeding.
MedLine Citation:
PMID:  22184636     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Glucocorticoids (GC) 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 may contribute to the development of type 2 diabetes mellitus (T2DM), although mechanisms 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 various indexes of insulin resistance that induces rapid-onset diabetes (ROD). Male Sprague-Dawley rats (aged 4 weeks) received exogenous corticosterone or wax (placebo) (4 x 100 mg each) pellets, implanted subcutaneously, and fed either a standard chow diet (SD) or a 60% high-fat diet (HFD) for 16 days (n= 8-10). Animals given corticosterone and a HFD (cort-HFD) had lower body weight (226.1±9.05 versus 358.9±5.57 g, mean ± SEM, p<0.05) and smaller relative glycolytic muscle mass (0.14±0.01 versus 0.09±0.02 g/kg body mass for the epitroclearis muscle, p<0.05), but increased relative epididymal mass (9.81±1.65 versus 4.56±0.54 g/kg, p<0.05), compared to controls (placebo-SD). Cort-HFD rats exhibited severe hepatic steatosis and increased muscle lipid deposition compared to 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 beta cell response (20% decrease) to oral glucose load compared to placebo-SD animals. Thus, a metabolic syndrome/T2DM phenotype can be rapidly induced in young Sprague-Dawley rats by using exogenous GCs if a HFD is consumed. This finding may be valuable in examining the physiological and molecular mechanisms of GC-induced metabolic disease.
Authors:
Yaniv Shpilberg; Jacqueline L Beaudry; Anna D'Souza; Jonathan E Campbell; Ashley Peckett; Michael C Riddell
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-19
Journal Detail:
Title:  Disease models & mechanisms     Volume:  -     ISSN:  1754-8411     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101483332     Medline TA:  Dis Model Mech     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
York University, Toronto, Ontario, Canada.
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