Blood amino acids concentration during insulin induced hypoglycemia in rats: the role of alanine and glutamine in glucose recovery

Abstract

Our purpose was to determine the blood amino acid concentration during insulin induced hypoglycemia (IIH) and examine if the administration of alanine or glutamine could help glycemia recovery in fasted rats. IIH was obtained by an intraperitoneal injection of regular insulin (1.0 U/kg). The blood levels of the majority of amino acids, including alanine and glutamine were decreased (P < 0.05) during IIH and this change correlates well with the duration than the intensity of hypoglycemia. On the other hand, the oral and intraperitoneal administration of alanine (100 mg/kg) or glutamine (100 mg/kg) accelerates glucose recovery. This effect was partly at least consequence of the increased capacity of the livers from IIH group to produce glucose from alanine and glutamine. It was concluded that the blood amino acids availability during IIH, particularly alanine and glutamine, play a pivotal role in recovery from hypoglycemia.

Oral Glutamine Dipeptide Prevents against Prolonged Hypoglycemia Induced by Detemir Insulin in Rats

“…Our previous study 9) demonstrated that the blood concentrations of L-alanine and L-glutamine were decreased during long term IIH. In agreement with this study, 9) we also demonstrated that oral glutamine dipeptide was able to promote glycemia recovery during long term IIH.…”

“…4) However, there are few studies in the prevention of nocturnal hypoglycemia. 5,6) Because rats show a suitable experimental model to study hypoglycemia [7][8][9][10] and considering the night habits of these animals, nocturnal IIH can be simulated with a diurnal pharmacological dose of Detemir insulin. Moreover, in spite the fact that glutamine dipeptide has been shown effective to promote acute glycemia recovery during long term IIH, 11) its rule to prevent prolonged hypoglycemia was not investigated.…”

“…Moreover, in spite the fact that glutamine dipeptide has been shown effective to promote acute glycemia recovery during long term IIH, 11) its rule to prevent prolonged hypoglycemia was not investigated. Thus, by using this rat model [7][8][9][10][11] we investigated if L-alanyl-L-glutamine peptide (glutamine dipeptide) could help against prolonged IIH. The choice of glutamine dipeptide was based in the following facts: 1) glutamine dipeptide results of the combination of the most abundant blood amino acid, i.e., L-glutamine 12) and the most important liver glucose precursor, i.e., L-alanine, 13) 2) very high doses of oral glutamine dipeptide did not show acute or subchronic toxicity, 14) 3) glutamine dipeptide overcomes the intestinal catabolism of Lglutamine, 15) 4) L-alanine from glutamine dipeptide catabolism stimulates the release of glucagon.…”

Evidence that L‐glutamine is better than L‐alanine as gluconeogenic substrate in perfused liver of weaned fasted rats submitted to short‐term insulin‐induced hypoglycaemia

“…However, it is important to remember that this conclusion data cannot easily be related to clinical practice, since L-glutamine is not stable in aqueous solution and its oral administration during short-term IIH did not promote glycaemia recovery probably as consequence of its intense catabolism by the enterocytes. 22,25,28 Furthermore, the present results suggest that to prevent hypoglycaemia, L-lactate or glycerol remain more efficient than L-glutamine, whether in COG or IIH weaned rats.…”

“…This experimental approach discards the influence of hepatic glycogen catabolism, changes in the hepatic blood flux and the variability of blood glucose precursors. 5,12 In contrast with adult hypoglycaemic rats in which the liver glucose production from L-alanine and L-lactate were increased, 22 the glucose production from these gluconeogenic substrates in livers from weaned hypoglycaemic rats was not affected by short-term IIH. On the other hand, like adult rats, 23,24 gluconeogenesis from L-glutamine which enters in this metabolic pathway after the pyruvate carboxylase step and before the phosphoenolpyruvate carboxykinase step 25 markedly rise in livers from shortterm IIH weaned rats.…”