ABSTRACT We investigated whether oral lactate could prevent seizures and deaths in mice with severe hypoglycemia induced by a high dose of insulin. For this purpose, mice were fasted for 15 h and then given an intraperitoneal injection of regular insulin (5.0 U/kg or 10.0 U/kg). Immediately after insulin injection, the mice received an oral dose of saline (control), glucose (5.5 mmol/kg), or lactate (18.0 mmol/kg). Glucose and lactate levels were measured in the blood and brain before and after the seizures began. Glucose and lactate delayed (p < 0.05) the onset of seizures associated with severe insulin-induced hypoglycemia. Elevated (p < 0.05) brain levels of lactate were associated with an absence of seizures in mice that received glucose or lactate, suggesting that lactate could prevent convulsions associated with severe insulin-induced hypoglycemia. However, the same oral dose of lactate that delayed the onset of convulsions also increased the mortality rate. In contrast, diazepam (3.0 mg/kg) prevented seizures and markedly decreased the frequency of death during severe insulin-induced hypoglycemia. The results demonstrated that in contrast to oral glucose, oral lactate intensifies insulin toxicity.

Em estudo recente empregando ratos Wistar com 6 h de privação alimentar demonstramos que ocorre ativação da neoglicogênese hepática durante a hipoglicemia induzida por insulina (HII). Neste estudo, os efeitos da administração intraperitoneal (ip) de glicose (100 mg/kg) sobre a ativação da neoglicogênese hepática durante a HII foi investigada. Assim, ratos com 6 h de privação alimentar que receberam insulina regular ip (1 U/kg) e 30 min depois salina (Grupo Controle) ou glicose ip (Grupo Experimental) foram comparados. Os experimentos foram executados 60 min após a injeção de insulina. A glicemia dos grupos Controle e Experimental não foi diferente (P > 0.05). Para investigar a neoglicogênese, realizouse experimentos de perfusão de fígado. Os resultados demonstraram, exceto para o glicerol, que fígados de ratos que receberam glicose ip (Grupo Experimental), apresentaram menor taxa (P < 0.05) de neoglicogênese a partir de L-alanina, Lglutamina, L-lactato ou L-alanina + L-glutamina + L-lactato + glicerol. Portanto, a ausência de recuperação da glicemia após administração de glicose foi mediada por inibição da neoglicogênese hepática.

The activation of hepatic gluconeogenesis in male Wistar adult 6 h fasted rats during insulin-induced hypoglycemia (IIH) was previously demonstrated. In this study, the effects of intraperitoneal (ip) glucose (100 mg/kg) on the activation of liver gluconeogenesis during IIH was investigated. Thus, 6 h fasted rats that received ip regular insulin (1 U/kg) and 30 min later ip saline (Control group) or glucose (Experimental group) were compared. All the experiments were executed 60 min after insulin injection. The glycemia of Control and Experimental groups were not different (P > 0.05). To investigate gluconeogenesis, liver perfusion experiments were performed. The results demonstrated that excepting glycerol, livers from rats which received ip glucose showed lower (P < 0.05) gluconeogenesis from L-alanine, L-glutamine, L-lactate or L-alanine + L-glutamine + L-lactate + glycerol. Therefore, the absence of glucose recovery after the glucose administration was mediated, at least in part, by an inhibition of hepatic gluconeogenesis.