Endogenous Substrates Utilized by Rat Brain in Severe Insulin‐Induced Hypoglycemia

Abstract

Several previous studies have demonstrated that severe hypoglycemia is accompanied by consumption of endogenous brain substrates (glycolytic and citric acid cycle metabolites and free amino acids) and some have shown a loss of structural components as well, notably phospholipids. In the present study, on paralysed and artificially ventilated rats, we measured cerebral oxygen and glucose consumption during 30 min of hypoglycemic coma (defined as hypoglycemia of sufficient severity to cause cessation of spontaneous EEG activity) and calculated the non‐glucose oxygen consumption. In an attempt to estimate the missing substrate we measured tissue concentrations of phospholipids and RNA. After 5 min of hypoglycemic coma, tissue phospholipid content decreased by about 8% with no further change during the subsequent 55 min. A similar reduction remained after 90 min of recovery, induced by glucose administration following 30 min of coma. Since no preferential loss of polyenoic fatty acids or of ethanolamine phosphoglycerides occurred, it is concluded that loss of phospholipids was due to phospholipase activity rather than to peroxidative degradation. The free fatty acid concentration increased sixfold after 5 min of coma and remained elevated during the course of hypoglycemia. A 9% reduction in tissue RNA content was observed after 30 min of hypoglycemia. Calculations indicated that available endogenous carbohydrate and amino acid substrates were essentially consumed after 5 min of coma, and that other non‐glucose substrates must have accounted for approximately 50μmol·g−1 of oxygen (8.3 μmol·g−1 in terms of glucose equivalents) within the 5–30 min period. The 10% reduction in phospholipid‐bound fatty acids was more than sufficient (in four‐ to fivefold excess) to account for this oxygen consumption. However, since no further degradation occurred in the 5–30 min period, there is no simple, direct, quantitative relationship between oxygen consumption and cortical fatty acid oxidation during this interval. The possibility thus remains that unmeasured exogenous or endogenous substrates were utilized.

Brain substrate utilisation during acute hypoglycaemia

“…Although glucose accounts for 90±92 % of the brain's oxidative metabolism during hypoglycaemia none of the substrates measured in our study were considered to account for the remaining 8±10 % of fuel utilisation of brain. Thus, the possibility may be considered that locally derived substrates, as suggested previously [32], or glycerol accounted for the small difference between glucose uptake and total oxidative metabolism of brain. In this context it is noteworthy that locally derived substrates are reported to be used by the rat brain during severe hypoglycaemia [32].…”

“…Thus, the possibility may be considered that locally derived substrates, as suggested previously [32], or glycerol accounted for the small difference between glucose uptake and total oxidative metabolism of brain. In this context it is noteworthy that locally derived substrates are reported to be used by the rat brain during severe hypoglycaemia [32]. In addition, glycogen in astrocytes has been suggested as a source of glucose for the brain under extreme conditions such as open heart surgery [33].…”

Membrane lipid changes in laminectomized and traumatized cat spinal cord.

“…Based upon our data, however, it is not possible at the present time to pinpoint their origins. The decreases seen in spinal cord FFA and acyl2Gro following the termination of compression may also be due to several mechanisms (42), including equilibration with the FFA in blood and cerebrospinal fluid, oxidation of the fatty acids as an energy source, reacylation into glycerophospholipids, and enzymic and nonenzymatic peroxidation of the polyunsaturated fatty acids (43)(44)(45)(46)(47).…”

“…Under continuous liquid nitrogen irrigation, :2 cm of spinal cord at the L2 site was maximally exposed and removed intact as described (25). Animals (14). The final lower phase was removed, evaporated under N2, and redissolved in 0.5 ml of chloroform/methanol, 1:1 (vol:vol).…”

“…However, certain pathological conditions, such as hypoglycemia, status epilepticus, hypoxia, ischemia, and cold injury, cause the levels of these compounds to rise dramatically (14)(15)(16)(17)(18)(19)(20)(21). No comparable values for FFA and acyl2Gro in either normal or traumatized spinal cord are currently available.…”