Effect of starvation on glutamine ammoniagenesis and gluconeogenesis in isolated mouse kidney tubules

Abstract

It has been shown recently that glutamine is taken up by the mouse kidney in vivo. However, knowledge about the fate of this amino acid and the regulation of its metabolism in the mouse kidney remains poor. Given the physiological and pathophysiological importance of renal glutamine metabolism and the increasing use of genetically modified mice in biological research, we have conducted a study to characterize glutamine metabolism in the mouse kidney. Proximal tubules isolated from fed and 48 h-starved mice and then incubated with a physiological concentration of glutamine, removed this amino acid and produced ammonium ions at similar rates. In agreement with this observation, activities of the ammoniagenic enzymes, glutaminase and glutamate dehydrogenase, were not different in the renal cortex of fed and starved mice, but the glutamate dehydrogenase mRNA level was elevated 4.5-fold in the renal cortex from starved mice. In contrast, glucose production from glutamine was greatly stimulated whereas the glutamine carbon removed, that was presumably completely oxidized in tubules from fed mice, was virtually suppressed in tubules from starved animals. In accordance with the starvation-induced stimulation of glutamine gluconeogenesis, the activities and mRNA levels of glucose-6-phosphatase, and especially of phosphoenolpyruvate carboxykinase, but not of fructose-1,6-bisphosphatase, were increased in the renal cortex of starved mice. On the basis of our in vitro results, the elevated urinary excretion of ammonium ions observed in starved mice probably reflected an increased transport of these ions into the urine at the expense of those released into the renal veins rather than a stimulation of renal ammoniagenesis.

Molecular mechanisms of glutamine action

“…In support of this observation, Ikeda and Iwata (2003) confirmed gluconeogenesis from glutamine in the kidney had a significant role in whole body glucose homeostasis. Conjard et al (2002), in a study with renal cortex isolated from fed and starved mice and incubated with glutamine, showed that the uptake of this amino acid and production of ammonium ions are similar in both groups. However, in starved mice, glucose production from glutamine was greatly stimulated as shown by the increase in activity and mRNA levels of glucose-6-phosphatase and especially of PEPCK, but not of fructose-1,6-biphosphatase.…”

“…Intracellular glutamine concentration varies between 2 and 20 mM (depending on cell type) whereas its extracellular concentration averages 0.7 mM (Newsholme et al, 2003b). Glutamine plays an essential role, promoting and maintaining function of various organs and cells such as kidney (Conjard et al, 2002), intestine (Lima et al, 1992;Ramos Lima et al, 2002), liver (de Souza et al, 2001), heart (Khogali et al, 2002), neurons (Mates et al, 2002), lymphocytes , macrophages , neutrophils Pithon-Curi et al, 2002a, 2003bPithon-Curi et al, 2003), pancreatic b-cells (Skelly et al, 1998), and white adipocytes (Curi et al, 1987;Kowalchuk et al, 1988). At the most basic level, glutamine serves as important fuel in these cells and tissues.…”

Enteral Feeding as a Part of Combination Treatment in a Patient after Small Intestine Transplantation

“…Энте ральный раствор, обладая химусоподобным действием, стимулирует моторику и улучшает процессы всасыва ния в тонкой кишке [7,8]. Глутамин является питатель ной средой для быстроделящихся клеток слизистой оболочки кишки, улучшая трофику и процессы всасы вания в тонкой кишке, антиоксиданты усиливают дан ный эффект, а трибутирин является энергетической со ставляющей [21][22][23][24][25][26][27][28][29][30]. В сочетании данные препараты в раннем послеоперационном периоде оказывают лечеб ное воздействие на трансплантированную кишку.…”

“…Известно, что использование глутамина способст вует снижению летальности и количества инфекцион ных осложнений [12,13,[21][22][23]. В исследовании у па циентов после трансплантации печени было выявлено положительное влияние глутамина на иммунный ста тус пациентов [17].…”

“…В исследовании у па циентов после трансплантации печени было выявлено положительное влияние глутамина на иммунный ста тус пациентов [17]. Глутамин является важным источ ником энергии и способствует поддержанию функций различных органов и клеток [23][24][25][26][27][28][29]. Высокая скорость поглощения глутамина характерна для быстро деля щихся клеток, таких как энтероциты, фибробласты и лимфоциты [21], в которых глутамин является важным предшественником пептидов и белков, а также амино сахаров, пуринов и пиримидинов, участвующих в син тезе нуклеотидов и нуклеиновых кислот [30].…”