Effects of alloxan diabetes, anti-insulin serum diabetes, and non-diabetic dehydration on brain carbohydrate and energy metabolism in young mice

Abstract

Alloxan-induced diabetes of 4 days duration produced metabolite changes in brain compatible with severe reduction in cerebral metabolism (phosphocreatine increased 70%), and reduced phosphofructokinase activity (fructose diphosphate levels fell 38%). There was a 56% reduction in brain lactate concentration, but pyruvate levels were unchanged. In 5 of 23 animals, brain glycogen levels increased; in the remainder blycogen levels decreased. Brain fructose concentration, 0.4 mmol/kg, was only 1/30 of the glucose concentration. The alloxan-treated animals were also severely dehydrated. Therefore, to determine the casual relation of insulin deficiency to these findings, the effects of chronic dehydration and acute insulin deficiency were investigated. Findings in the brains of severely dehydrated animals (water deprivation and mannitol injections for 4 days) were almost identical with those seen after alloxan treatment. The exceptions were that, in the dehydrated mice, reductions in lactate and pyruvate were proportional, and glycogen levels were consistently reduced. In acute diabetes (6 to 24 hours after repeated anti-insulin serum injections) P-creatine, fructose diphosphate, and lactate levels were normal. Pyruvate levels were normal at 6 hours, but increased 39% by 12 to 24 hours; glycogen was 36% higher at 6 hours and 63% at 12 to 24 hours. Insulin (and glucose) appeared to be specific in correcting the metabolic abnormalities found in the brains of animals with alloxan-induced diabetes. At 4 and one half hours after treatment with insulin and glucose, glucose 6-phosphate levels fell 25%, fructose diphosphate increased 28%, and lactate and the lactate to pyruvate ratio returned to normal; glycogen increased 50%. However, the treatment also had a dramatic clinical effect. Since animals gained 8 to 27% of body weight during therapy, at least some of the improvements in metabolite levels could be related to rehydration.