Impact of STZ-induced hyperglycemia and insulin-induced hypoglycemia in plasma amino acids and cortical synaptosomal neurotransmitters.
In this work, we evaluated the effects of streptozotocin (STZ)-induced hyperglycemia and an acute episode of insulin-induced hypoglycemia in plasma amino acids and cortical neurotransmitters. For that purpose, we used citrate (vehicle)-treated Wistar rats, STZ-treated rats [i.p., 50 mg/kg body weight], and STZ-treated rats injected with insulin [s.c., dose adjusted with blood glucose levels] 1 h prior to sacrifice to induce an acute episode of hypoglycemia. Plasma was collected for determination of amino acids levels. In addition, cortical synaptosomal preparations were obtained and the total levels of neurotransmitters, levels of aspartate, glutamate, taurine, and GABA released by the action of KCl, iodoacetic acid (IAA), ouabain, and veratridine, membrane potential and ATP levels were evaluated. Compared with control rats, plasma from hypoglycemic rats presented increased levels of aspartate, glutamate, glutamine, and taurine whereas GABA levels were decreased in STZ and hypoglycemic rats. Similarly, glutamate and taurine levels were increased in hypoglycemic synaptosomes while GABA decreased in hypoglycemic and STZ-diabetic synaptosomes. The depolarizing agent KCl promoted an increase in aspartate, glutamate, and taurine release from hypoglycemic synaptosomes. The highest release of neurotransmitters occurred in the presence of veratridine and ouabain, two other depolarizing agents, in all groups of experimental animals. However, a higher release of glutamate was observed in the diabetic and hypoglycemic synaptosomes. No alterations were observed in synaptosomal membrane potential and ATP levels. These results show that in the presence of a metabolic insult a higher release of excitatory amino acids occurs, which may underlay the neuronal injury observed in type 1 diabetic patients under insulin therapy.
Cardoso
Susana
S
Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
Carvalho
Cristina
C
Santos
Renato
R
Correia
Sónia
S
Santos
Maria S
MS
Seiça
Raquel
R
Oliveira
Catarina R
CR
Moreira
Paula I
PI
D000596:Amino Acids / Q000097:blood*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000097:blood / Q000209:etiology* / Q000473:pathology; D007003:Hypoglycemia / Q000097:blood / Q000209:etiology* / Q000473:pathology; D008297:Male; D018377:Neurotransmitter Agents / Q000097:blood* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism* / Q000473:pathology*
D000596:Amino Acids; D018377:Neurotransmitter Agents