BACKGROUND AND AIMS: Not only a sustained hyperglycemic state, but also a fluctuating plasma glucose concentration has been implicated in the derangement of brain energy metabolism. Acute hyperglycemia is not thought to alter the cerebral metabolic rate of glucose (CMRglc). However, whether chronic hyperglycemia enhances or suppresses the CMRglc remains controversial, and the effect of a fluctuating plasma glucose concentration on the CMRglc has not been examined extensively. Astrocytes are thought to be more dependent on glycolytic, rather than oxidative, glucose metabolism for energy production. Recent findings, however, have revealed that oxidative metabolism in astrocytes might be comparable to that in neurons in vivo. Recently, we reported that oxidative metabolism in astrocytes depended on the environmental glucose concentration in vitro (Abe et al., JCBF&M 26: 153-160, 2006). In the present study, we examined the effects of short-term exposure to a high glucose concentration on the oxidative metabolism of astroglias, as assessed by the oxidation of [14C]lactate or [14C]acetate. METHODS: Primary cultures of neurons or secondary cultures of astroglia were prepared from SD rats, as described previously (Takahashi et al, PNAS 92: 4616-4620, 1995). The cells were cultured in the presence of a high (22 mM) or low (5 mM) concentration of glucose. Twenty-four hours prior to the 14C assay, the culture media of replaced with media containing a high (22 mM) or low (5 mM) concentration of glucose and the cells were further incubated for 24 hours. On the day of the assay, the cells were washed twice with PBS without glucose and were assayed for [14C]deoxyglucose phosphorylation and [14C]lactate or [14C]acetate oxidation. RESULTS: The high or low glucose media did not alter the rates of [14C]deoxyglucose phosphorylation. The low glucose medium increased the oxidation of [14C]lactate only in astroglia, as evidenced by the increased production of 14CO2. Twenty-four-hour exposure to a high glucose concentration resulted in a significant decrease in [14C]lactate oxidation in the astroglia (2.9 ± 0.5 pmol lactate/μg protein/60 min, mean ± SD, n=4), compared with that in cells cultured in the presence of a low glucose concentration (4.8 ± 0.4, p < 0.001). In contrast, 24-hour exposure to a low glucose concentration after cultivation in a high glucose medium did not affect [14C]lactate oxidation in the astroglia. [14C]acetate, an astrocyte-specific reporter molecule was also employed. [14C]acetate oxidation in neurons was negligible. [14C]acetate oxidation in the astroglia that were cultured in a high glucose medium (1.7 ± 0.1 pmol acetate/μg protein/60 min, n=4) was lower than that in the cells that were cultured in a low glucose medium (2.8 ± 0.4). Similarly, 24-hour exposure to a high glucose medium significantly reduced [14C]acetate oxidation from 1.9 ± 0.3 to 1.2 ± 0.3 (p < 0.05). CONCLUSIONS: Fluctuations in the environmental glucose concentration do not alter glucose metabolism in neurons. In contrast, increasing the concentration of glucose, either acutely or chronically, suppressed oxidative metabolism in astroglia. These different responses of neurons and astroglia may shed new light on brain energy metabolism in diabetic patients with fluctuating plasma glucose concentrations.
|Journal||Journal of Cerebral Blood Flow and Metabolism|
|Issue number||SUPPL. 1|
|Publication status||Published - 2007 Nov 13|
ASJC Scopus subject areas
- Clinical Neurology
- Cardiology and Cardiovascular Medicine