Brain glucose utilization and transport and cortical function in chronic vs. acute hypoglycemia

Abstract

We compared regional brain capillary permeability-surface area products for glucose transfer (PSin), cerebral glucose utilization (rCMRGlc) rates, and brain tissue glucose levels (GlCbr) in N2O-sedated, paralyzed, and artificially ventilated rats during normoglycemia (NG), insulin-induced acute hypoglycemia (AH), or chronic hypoglycemia (CH) [hypoglycemic plasma glucose (Glcp) = 2.2-2.3 mumol/ml]. In addition, a comparative assessment of brain function in AH vs. CH was performed employing somatosensory-evoked response (SSER) technology. A double-label (3H and 14C) 2-deoxy-D-glucose method was used for the simultaneous assessment of PSin and rCMRGlc. Compared with normoglycemic controls, AH resulted in significant 40-50% reductions in rCMRGlc in 10 of 11 regions analyzed (cerebellum unchanged). In CH vs. AH, significantly higher values for rCMRGlc, Glcbr/Glcp ratios, and PSin were seen in 8, 8, and 5 regions, respectively. No differences in rCMRGlc were observed when comparing CH vs. NG groups. Furthermore, CH rats were able to sustain normal SSER at levels of hypoglycemia (1.5 mumol/ml) that, when imposed acutely, resulted in attenuated SSER. Thus CH is associated with an enhanced blood-brain glucose transport capacity in many (but not all) brain regions. This in turn increases rCMRGlc and improves the general cerebral function compared with that seen during AH.