Abstract
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.
Highlights
Insulin-induced hypoglycemia, the major acute adverse effect of insulin therapy (Sanches et al, 2013; Vilela et al, 2014), is clinically relevant because glucose is the main fuel for the brain (Bazzigaluppi et al, 2017)
Because glucose administration has an evanescent effect in treating hypoglycemia, diabetes patients must be advised to eat regular meals to prevent a recurrence of insulin-induced hypoglycemia
The mice were them observed for a period of 300 min, which started immediately after an ip dose of insulin followed by an oral dose of saline, lactate or glucose
Summary
Insulin-induced hypoglycemia, the major acute adverse effect of insulin therapy (Sanches et al, 2013; Vilela et al, 2014), is clinically relevant because glucose is the main fuel for the brain (Bazzigaluppi et al, 2017). Because glucose administration has an evanescent effect in treating hypoglycemia, diabetes patients must be advised to eat regular meals to prevent a recurrence of insulin-induced hypoglycemia. During sleep, this method is not adequate to treat nocturnal hypoglycemia. Nocturnal hypoglycemia associated with “dead in bed syndrome” is responsible for 5-6% of deaths among patients with type 1 diabetes (Weston, 2012). It is necessary replace glucose with substances that are more potent and have prolonged effects. The blood and brain levels of glucose and lactate, and the ability of diazepam to prevent seizures and deaths were evaluated
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