Md. Thompson et al., The effect of chronic dexamethasone-induced hyperglycemia and its acute treatment with insulin on grain glucose and glycogen concentrations in rats, ANESTHESIOL, 93(5), 2000, pp. 1279-1284
Citations number
22
Categorie Soggetti
Aneshtesia & Intensive Care","Medical Research Diagnosis & Treatment
Background: In the rat model of forebrain Ischemia, long-term dexamethasone
treatment is reported to cause hyperglycemia and worsen postischemic funct
ional and histologic injury. This effect was assumed to result from glucose
enhancement of intraischemic lactic acidosis within the brain. Short-term
insulin therapy restored normoglycemia but did not return histologic injury
completely to baseline values. Using a nonischemic rat model, the current
study attempted to identify a metabolic basis for such outcome data.
Methods: Fifty-eight halothane-anesthetized (1.3% inspired) Sprague-Dawley
rats were assigned randomly to be administered either no treatment (N = 18)
or 2 mg/kg intraperitoneal dexamethasone (N = 40). The latter were adminis
tered dexamethasone 3 h before the study only (N = 8) or for 3 h before the
study plus daily for 1 day (N = 8), 2 days (N = 8), or 4 days (N = 16), Of
the rats treated with dexamethasone for 4 days, one half(N = 8) were admin
istered an insulin-containing saline infusion subsequently to restore normo
glycemia short-term All other rats (N = 50) were administered an infusion o
f saline without insulin. Plasma glucose was quantified and brains were exc
ised after In situ freezing. Brain glucose and glycogen concentrations were
measured using enzymatic fluorometric analyses.
Results After 4 days of dexamethasone treatment, plasma glucose was 159% gr
eater than in rats administered placebo (i.e., 22.01 +/- 4.66 vs. 8.51 +/-
1.65 mu mol/ml; mean +/- SD; P < 0.0001). Brain glucose concentrations incr
eased parallel to plasma glucose, An insulin infusion for 27 +/- 5 min rest
ored normoglycemia but resulted In a brain-to-plasma glucose ratio that was
32% greater than baseline values (P < 0.01), Neither dexamethasone nor the
combination of dexamethasone plus insulin affected brain glycogen concentr
ations.
Conclusions In a nonischemic rat model, dexamethasone alone had no Independ
ent effect on the brain-to-plasma glucose ratio. However, short-term insuli
n therapy caused a dysequilibrium between plasma and brain glucose, resulti
ng in an underestimation of brain glucose concentrations when normoglycemia
was restored. The dysequilibrium likely was caused by the rapid rate of gl
ucose reduction, The magnitude of the effect may account for the failure of
insulin to reverse dexamethasone enhancement of neurologic injury complete
ly Ln a previous report that used the rat model of forebrain Ischemia.