Format

Send to

Choose Destination
Dis Model Mech. 2012 Sep;5(5):681-5. doi: 10.1242/dmm.009035. Epub 2012 Aug 3.

Fasting hyperglycemia in the Goto-Kakizaki rat is dependent on corticosterone: a confounding variable in rodent models of type 2 diabetes.

Author information

1
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.

Abstract

The Goto-Kakizaki (GK) rat is an inbred model of type 2 diabetes (T2D); GK rats are lean but have hyperglycemia and increased gluconeogenesis. However, fasting hyperglycemia in other commonly used rodent models of T2D is associated with increased corticosterone, and thus the underlying mechanism for hyperglycemia differs significantly from T2D in humans. Information regarding corticosterone in the GK rat is not readily available. We studied 14- to 16-week-old GK rats in comparison with age-matched control Wistar-Kyoto (WK) rats. GK rats had lower body weights (WK: 343±10 g vs GK: 286±9 g, P<0.01), but higher plasma glucose concentrations (WK: 132±1.5 mg/dl vs GK: 210±11.7 mg/dl, P<0.01). This was associated with an ∼twofold increase in PEPCK1 expression (P<0.05). However, these findings were also associated with elevations in plasma corticosterone and urinary corticosterone excretion. Ketoconazole (KTZ) treatment in GK rats reduced plasma corticosterone, fasting glucose (GK: 218±15 mg/dl vs GK-KTZ: 135±19 mg/dl, P<0.01) and rates of glucose production [GK: 16.5±0.6 mg/(kg-minute) vs GK-KTZ: 12.2±0.9 mg/(kg-minute), P<0.01]. This was associated with an ∼40% reduction in hepatic PEPCK1 expression as well as a 20% reduction in alanine turnover. Thus, hypercorticosteronemia might contribute to the diabetic phenotype of GK rats and should be considered as a potential confounder in rodent models of T2D.

PMID:
22864022
PMCID:
PMC3424465
DOI:
10.1242/dmm.009035
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center