Reduction of Hepatic and Adipose Tissue Glucocorticoid Receptor Expression With Antisense Oligonucleotides Improves Hyperglycemia and Hyperlipidemia in Diabetic Rodents Without Causing Systemic Glucocorticoid Antagonism

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FIG. 1.
FIG. 1.

In vitro reduction of GCCR mRNA expression in mouse and rat hepatocytes. Mouse (A) or rat (B) primary hepatocytes were treated with the indicated ASO concentration for 4 h as described in research design and methods. After ASO treatment, cells were cultured in growth medium for an additional 16–20 h. Total RNA was extracted and GCCR mRNA expression was assessed by RT-PCR. GCCR expression was normalized to total RNA in the same samples. Data are expressed as means ± SE of mRNA levels relative to untreated cells (n = 3). *P < 0.05, GCCR ASO treatment vs. corresponding untreated group by ANOVA. C: GCCR ASO specifically reduces GCCR mRNA levels in liver from ob/ob mice. Mice were dosed with saline, GCCR ASO 6.25 mg/kg, 12.5 mg/kg, and 25 mg/kg, or control ASO 25 mg/kg subcutaneously twice a week for 4 weeks. Total mRNA was prepared and analyzed for GCCR expression by RT-PCR (n = 7 per group). Data are expressed as means ± SE relative to saline-treated mice. *P < 0.05, GCCR ASO treatment vs. saline treatment by ANOVA. D: Reduction of GCCR expression lowers plasma glucose. Ob/ob mice were dosed as described above, and plasma was analyzed for glucose as described in research design and methods. Data are expressed as means ± SE. *P < 0.05, GCCR ASO treatment vs. saline treatment by ANOVA.

This Article

  1. Diabetes vol. 54 no. 6 1846-1853