Oral Glutamine Is Superior Than Oral Glucose to Promote Glycemia Recovery in Mice Submitted to Insulin-Induced Hypoglycemia

Abstract

The effect of the oral administration of blood glucose precursors on glycemia recovery and liver glucose production in fasted mice subjected to insulin-induced hypoglycemia (IIH) was investigated. IIH was obtained with increasing doses (from 0.5 to 2.0 U·kg−1) of intraperitoneal regular insulin where glycemia was evaluated from 0 to 300 min after insulin injection. The dose of 1.0 U·kg−1 showed the best results, that is, a clear glycemia recovery phase without convulsions or deaths. Thus, this dose was used in all experiments. Afterwards, mice submitted to IIH received orally by gavage: saline (control group), glucose (100 mg·kg−1), glycerol (100 mg·kg−1), lactate (100 mg·kg−1), alanine (100 mg·kg−1), or glutamine (100 mg·kg−1). It was observed that glutamine was more effective in promoting glycemia recovery if compared with glucose, lactate, glycerol, or alanine. In agreement with these results, the best performance in terms of liver glucose production was obtained when glutamine was used as glucose precursors. These results open perspectives for clinical studies to investigate the impact of oral administration of gluconeogenic amino acids to promote glycemia recovery during hypoglycemia.

Insulin degludec and glutamine dipeptide modify glucose homeostasis and liver metabolism in diabetic mice undergoing insulin-induced hypoglycemia

“…This similar fact has also been found in patients and rodents with type 2 diabetes and T1D (Bataglini et al, 2017;Chakera et al, 2018). The blood glucose of fasted normoglycemic mice also drops sharply 60 min after IIH but it recovers almost completely after 300 min (Nunes Santiago et al, 2013). In the present study, only a relatively poor response to hypoglycemia was observed in T1D mice receiving cortisol.…”

“…After 30-day treatment, 15 h fasted control and T1D mice received regular insulin to induce IIH and cortisol 15 min later. One hour after IIH, the non-recirculating liver perfusion was performed as previously described (Broetto-Biazon et al, 2009;Nunes Santiago et al, 2013). After an initial period of 10 min of perfusion to stabilize the preparation, samples of the effluent perfusion fluid were collected at five-minute intervals and analyzed for their content of glucose, lactate, pyruvate, ammonia and urea (Bergmeyer, 1974).…”

“…Glutamine is also a relevant substrate for hepatic gluconeogenesis, a crucial metabolic pathway for euglycemic maintenance after glycogen depletion during fasting and hypoglycemic episodes (Cruzat et al, 2018). In this regard, normoglycemic mice, but not T1D mice, orally receiving glutamine shortly after the IIH had higher hepatic gluconeogenesis and greater ability to recover blood glucose than mice receiving alanine or even glucose (Bataglini et al, 2017;Nunes Santiago et al, 2013). However, it is not known if long-term supplementation with glutamine attenuates episodes of IIH in T1D mice.…”

Metabolismo Do Lactato E Avaliação De Desempenho: Dois Lados Do Mesmo Processo

“…nesse sentido, é interessante observar que no fígado, um órgão essencial para a reutilização de lactato sanguíneo como fonte de energia (por meio da gliconeogênese), a produção de glicose a partir de lactato aumenta rapidamente para concentrações de lactato entre 0,5 e 4 mM, mas tende a se estabilizar entre 4 e 16 mM (SAnTIAGO et al, 2013). Sendo assim, a capacidade gliconeogênica hepática, a partir de lactato, poderia ter papel importante no estabelecimento do LAn e na sua alteração com o treinamento.…”

Oral lactate intensifies insulin toxicity during severe insulin-induced hypoglycemia in mice

“…In this regard, the effects of glucose have previously been compared with those of glutamine, alanine, lactate, and pyruvate (Galende et al, 2009;Hartman et al, 2010;Nunes Santiago et al, 2013;Rodrigues et al, 2011).…”