Supplementation with L-Glutamine and L-Alanyl-L-Glutamine Changes Biochemical Parameters and Jejunum Morphophysiology in Type 1 Diabetic Wistar Rats

Abstract

We evaluated the effects of the supplementation with L-glutamine and glutamine dipeptide (GDP) on biochemical and morphophysiological parameters in streptozotocin-diabetic rats. For this purpose, thirty animals were distributed into six groups treated orally (gavage) during thirty days: non diabetic rats (Control) + saline, diabetic + saline; Control + L-glutamine (248 mg/kg), Diabetic + L-glutamine (248 mg/kg), Control + GDP (400 mg/kg), Diabetic + GDP (400 mg/kg). Diabetes was induced by an intravenous injection of streptozotocin (60 mg/kg) and confirmed by fasting glucose ≥ 200 mg/dL. Physiological parameters, i.e., body mass, food intake, blood glucose, water intake, urine and faeces were evaluated during supplementation. After the period of supplementation, the animals were euthanized. The blood was collected for biochemical assays (fructosamine, transaminases, lipid profile, total protein, urea, ammonia). Moreover, the jejunum was excised and stored for morphophysiological assays (intestinal enzyme activity, intestinal wall morphology, crypt proliferative index, number of serotoninergic cells from the mucosa, and vipergic neurons from the submucosal tunica). The physiological parameters, protein metabolism and intestinal enzyme activity did not change with the supplementation with L-glutamine or GDP. In diabetic animals, transaminases and fructosamine improved with L-glutamine and GDP supplementations, while the lipid profile improved with L-glutamine. Furthermore, both forms of supplementation promoted changes in jejunal tunicas and wall morphometry of control and diabetic groups, but only L-glutamine promoted maintenance of serotoninergic cells and vipergic neurons populations. On the other hand, control animals showed changes that may indicate negative effects of L-glutamine. Thus, the supplementation with L-glutamine was more efficient for maintaining intestinal morphophysiology and the supplementation with GDP was more efficient to the organism as a whole. Thus, we can conclude that local differences in absorption and metabolism could explain the differences between the supplementation with L-glutamine or GDP.

Glutamine or Glutamine Dipeptide Supplementation Improves Gluconeogenesis and Liver Glycogenosis in Type 1 Diabetic Rats

“…These alterations can favor the appearance of lipid infiltrations in the hepatic tissue [40], a condition known as hepatic steatosis. However, the fact that the disease decreases the normal lipid content of the liver can be due to the enhanced peripheral use, which would result in increased VLDL, as also observed by Rosa et al [19]. Although GLN did not change this parameter, GDP increased these infiltrations to levels similar to group GC.…”

“…Differently, GLN supplementation increased gluconeogenesis from glycerol, which was decreased by diabetes, in group GDGLN. This shift of glycerol to glucose synthesis could be responsible for the decreased plasmatic TGL and VLDL observed by Rosa et al [19]. This was not observed in the group supplemented by GDP, and despite plasmatic TGL and VLDL not being changed by GDP supplementation [19], the rats of this study had an increased lipid infiltration in the hepatic parenchyma that could result from the enhanced esterification of TGL and production of VLDL.…”

“…Dyslipidemias are common in diabetic individuals, as experimentally demonstrated by Rosa et al [19] and Tronchini et al [39]. These alterations can favor the appearance of lipid infiltrations in the hepatic tissue [40], a condition known as hepatic steatosis.…”

“…Although the supplementation with GLN or GDP did not change the number and area of the hepatocytes, the amount of glycogen was decreased by 35% in the supplemented groups. Experiments from Rosa et al [19] show the capacity of glutamine in decreasing the blood concentrations of AST and ALT that are increased by diabetes. In addition, there is a correlation between the increased plasmatic values of AST and ALT and the glycogen content of hepatocytes [38].…”

“…Diabetes was induced by the intravenous injection of streptozotocin (STZ) at the dose of 60 mg/kg (Sigma ® , St. Louis, EUA) dissolved in 10 mM citrate buffer pH 4.5. After seven days, the animals having fasting blood glucose ≥ 200 mg/dL were considered diabetic [19].…”